<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03020160</url>
  </required_header>
  <id_info>
    <org_study_id>BO39182</org_study_id>
    <secondary_id>2016-001094-33</secondary_id>
    <nct_id>NCT03020160</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks in Participants With Hemophilia A</brief_title>
  <acronym>HAVEN 4</acronym>
  <official_title>A Multicenter, Open-Label, Phase III Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks (Q4W) in Patients With Hemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chugai Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This multicenter, open-label, non-randomized study will assess the efficacy, safety,&#xD;
      pharmacokinetics, and pharmacodynamics of emicizumab administered at a dose of 6 milligrams&#xD;
      per kilogram (mg/kg) every 4 weeks in participants with hemophilia A with or without&#xD;
      inhibitors against factor VIII (FVIII). The study consists of 2 parts: a pharmacokinetic (PK)&#xD;
      run-in part followed by an expansion part.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Actual">June 29, 2022</completion_date>
  <primary_completion_date type="Actual">December 15, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Bleeds</measure>
    <time_frame>From Baseline to at least 24 weeks</time_frame>
    <description>The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a &quot;treated bleed&quot; if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a &quot;treatment for bleed&quot;, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Expansion Part: Annualized Bleeding Rate (ABR) for All Bleeds</measure>
    <time_frame>From Baseline to at least 24 weeks</time_frame>
    <description>The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As &quot;all bleeds&quot; comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the &quot;treated bleeds&quot; outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds</measure>
    <time_frame>From Baseline to at least 24 weeks</time_frame>
    <description>The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as &quot;spontaneous&quot; if there is no other known contributing factor such as trauma or procedure/surgery. A &quot;treated spontaneous bleed&quot; is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Joint Bleeds</measure>
    <time_frame>From Baseline to at least 24 weeks</time_frame>
    <description>The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;joint bleed&quot; is defined as a bleed with type reported as &quot;joint&quot; and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A &quot;treated joint bleed&quot; is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of joint bleeds, excluding bleeds due to surgery/procedure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds</measure>
    <time_frame>From Baseline to at least 24 weeks</time_frame>
    <description>The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;target joint bleed&quot; is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A &quot;treated target joint bleed&quot; is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Change From Baseline to Week 25 in the Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score for Adult Participants (≥18 Years of Age)</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Total Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Change From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score for Adult Participants (≥18 Years of Age)</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Change From Baseline to Week 25 in the Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Total Score for Adolescent Participants (12-17 Years of Age)</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The Haemo-QoL-SF was developed in a series of age-related questionnaires to measure health-related quality of life (HRQoL) in children and adolescents with hemophilia. The short version for older children containing 35 items was selected for adolescents in this study. Items are rated along five response options: never, rarely, sometimes, often, or all the time. This version covers nine dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia, and treatment). Scale scores range from 0 to 100, with lower scores indicating better HRQoL. Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Change From Baseline to Week 25 in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire VAS Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Change From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</measure>
    <time_frame>Baseline, Week 25</time_frame>
    <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Proportion of Days Away From Work to Expected Days at Work in the Previous Four Weeks</measure>
    <time_frame>Predose at Baseline, Weeks 13 and 25</time_frame>
    <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from work (i.e., days of work missed) and the expected number of days at work in the previous four weeks, which is reported here for each time point as the proportion of the number of days away from work to the expected number of days at work.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Proportion of Days Away From School to Expected Days at School in the Previous Four Weeks</measure>
    <time_frame>Predose at Baseline, Weeks 13 and 25</time_frame>
    <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from school (i.e., days of school missed) and the expected number of days at school in the previous four weeks, which is reported here as the proportion of the number of days away from school to the expected number of days at school.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Number of Days Hospitalized</measure>
    <time_frame>From Baseline until at least 24 weeks of treatment (median [min-max] observation time: 25.57 [24.1-29.4] weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Percentage of Participants Who Preferred Either the New Emicizumab Subcutaneous (SC) Treatment or Their Previous Hemophilia Intravenous (IV) Treatment, or Had No Preference, as Assessed Using the Emicizumab Preference Survey</measure>
    <time_frame>Predose at Week 17</time_frame>
    <description>The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with intravenous (IV) factor VIIII (FVIII) or subcutaneous (SC) emicizumab, or no preference.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Apparent Plasma Terminal Half-Life (t1/2) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab</measure>
    <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
    <description>Only CL/F is reported after the first dose; the apparent clearance at steady state (CLss/F) is reported after the sixth dose instead. This is because t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule, and dependent PK parameters, such as CL/F, could not be estimated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Run-In Part: Plasma Concentration of Emicizumab at Specified Timepoints</measure>
    <time_frame>Week 1 Day 1 predose and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 6, 7, 8, 9, 11, 13, 15, 17, 19, 21, 22, 23, 24, and 25, and every 12 weeks thereafter to Week 265</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expansion Part: Plasma Concentration of Emicizumab at Specified Timepoints</measure>
    <time_frame>Predose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 37, 49, 61, 73. 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, and 253</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Adverse Event</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>The number of participants experiencing at least one adverse event (AE), including all non-serious and serious AEs, is reported here. According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Grade ≥3 Adverse Event</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>The World Health Organization (WHO) Toxicity Grading Scale was used for assessing adverse event (AE) severity. For AEs that are not specifically listed in the WHO Toxicity Grading Scale, a Grade 3 AE is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a Grade 4 AE is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE; the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Adverse Event Related to Study Treatment</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>According to the ICH guideline for Good Clinical Practice, an adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. In order to assess the causality of an AE, investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE is considered to be related to the study drug, indicating &quot;yes&quot; or &quot;no&quot; accordingly.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Shift in Clinical Laboratory Parameters From Baseline World Health Organization (WHO) Toxicity Scale Grade 0-2 to Post-Baseline WHO Grade 3 or 4</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. In this study, any laboratory value changes were transient and returned to baseline for all participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Local Injection-Site Reaction</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an &quot;injection-site reaction&quot; on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a &quot;local injection-site reaction.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Thromboembolic Event</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>Hypercoagulation and thromboembolic events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers educated patients/caregivers to recognize the signs and symptoms of potential thromboembolism (i.e., dyspnea, chest pain, leg pain or swelling, etc.) and to ensure that they understood the importance of seeking appropriate medical attention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Thrombotic Microangiopathy</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>Thrombotic microangiopathy is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, or central nervous system, etc. Thrombotic microangiopathy events were to be reported as serious adverse events or adverse events of special interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction</measure>
    <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
    <description>Since emicizumab is a biological product, acute, systemic hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. These events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers (HCP) instructed patients and caregivers how to recognize the signs and symptoms of hypersensitivity, anaphylactic, and anaphylactoid reactions and to contact an HCP or seek emergency care in case of any such occurrence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Drug Antibodies to Emicizumab at Any Time Post-Baseline During the Study</measure>
    <time_frame>Baseline, Weeks 5, 9, 13, 17, 21, and 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)</time_frame>
    <description>A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) to emicizumab in blood plasma samples. Participants were considered ADA-positive if they were ADA-negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ADA response).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With De Novo Development of Anti-Factor VIII (FVIII) Antibodies</measure>
    <time_frame>Baseline, Weeks 9 and 17 (for non-inhibitor subjects only), Week 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)</time_frame>
    <description>The levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</measure>
    <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
    <description>The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</measure>
    <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
    <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</measure>
    <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
    <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</measure>
    <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
    <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Hemophilia A</condition>
  <arm_group>
    <arm_group_label>Emicizumab: PK Run-in Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks, with no loading dose, for at least 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Emicizumab: Expansion Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks for at least 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Emicizumab</intervention_name>
    <description>Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.</description>
    <arm_group_label>Emicizumab: Expansion Cohort</arm_group_label>
    <arm_group_label>Emicizumab: PK Run-in Cohort</arm_group_label>
    <other_name>Hemlibra</other_name>
    <other_name>RO5534262</other_name>
    <other_name>ACE910</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body weight greater than or equal to (&gt;/=) 40 kilograms (kg) at screening&#xD;
&#xD;
          -  Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors&#xD;
&#xD;
          -  Participants using rFVIIa or willing to switch to recombinant activated factor VII&#xD;
             (rFVIIa) as primary bypassing agent for the treatment of breakthrough bleeds&#xD;
&#xD;
          -  FVIII inhibitor test during screening with titer results available prior to first&#xD;
             administration of study drug&#xD;
&#xD;
          -  Participants without FVIII inhibitors, that is with less than (&lt;) 0.6 Bethesda unit&#xD;
             per milliliter [BU/mL];&lt; 1.0 BU/mL only for laboratories with an historical&#xD;
             sensitivity cutoff for inhibitor detection of 1.0 BU/mL, who completed successful&#xD;
             immune tolerance induction (ITI) must have done so at least 5 years before screening&#xD;
             and must have no evidence of inhibitor recurrence (permanent or temporary) indicated&#xD;
             by detection of an inhibitor greater than (&gt;) 0.6 BU/mL (&gt; 1.0 BU/mL only for&#xD;
             laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0&#xD;
             BU/mL) since ITI&#xD;
&#xD;
          -  Adequate hematologic, hepatic, and renal function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inherited or acquired bleeding disorder other than hemophilia A&#xD;
&#xD;
          -  Ongoing or planned ITI therapy; participants in whom ITI has failed will be eligible&#xD;
             with a 72-hour washout period prior to the first emicizumab administration&#xD;
&#xD;
          -  History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the&#xD;
             investigator's judgment&#xD;
&#xD;
          -  Participants who are at high risk for thrombotic microangiopathy (TMA) (for example,&#xD;
             have a previous medical or family history of TMA), in the investigator's judgment&#xD;
&#xD;
          -  Previous (within the last 12 months) or current treatment for thromboembolic disease&#xD;
             (with the exception of previous catheter-associated thrombosis for which&#xD;
             anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease&#xD;
&#xD;
          -  Other conditions (for example, certain autoimmune diseases) that may currently&#xD;
             increase the risk of bleeding or thrombosis&#xD;
&#xD;
          -  History of clinically significant hypersensitivity associated with monoclonal antibody&#xD;
             therapies or components of the emicizumab injection&#xD;
&#xD;
          -  Known HIV infection with cluster of differentiation (CD) 4 cells counts &lt;200 cells per&#xD;
             microliter (cells/mcL)&#xD;
&#xD;
          -  Use of systemic immunomodulators (for example, interferon) at enrollment or planned&#xD;
             use during the study, with the exception of anti-retroviral therapy&#xD;
&#xD;
          -  Concomitant disease, condition, significant abnormality on screening evaluations or&#xD;
             laboratory tests, or treatment that could interfere with the conduct of the study, or&#xD;
             that would, in the opinion of the investigator, pose an additional unacceptable risk&#xD;
             in administering study drug to the participant&#xD;
&#xD;
          -  Pregnancy or lactation or intention to become pregnant during the study&#xD;
&#xD;
          -  Women with a positive serum pregnancy test result within 7 days prior to initiation of&#xD;
             study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Hemophilia &amp; Thrombosis center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan, C.S. Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ of N Carolina Chapel Hill; Hematology/Oncology</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane Hospital; Clinical Haematology</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital; Haematology Clinical Trials</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires St-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital</name>
      <address>
        <city>Hokkaido</city>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nara Medical University Hospital</name>
      <address>
        <city>Nara</city>
        <zip>634-8522</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Center for Child Health and Development</name>
      <address>
        <city>Tokyo</city>
        <zip>157-8535</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Medical University Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>160-0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych</name>
      <address>
        <city>Warsaw</city>
        <zip>02-776</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku</name>
      <address>
        <city>Wrocław</city>
        <zip>50-367</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Paz; Servicio de Hematologia</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio; Servicio de Hematologia</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Fe; Servicio de Hematologia</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Japan</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>December 4, 2018</results_first_submitted>
  <results_first_submitted_qc>December 4, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 26, 2018</results_first_posted>
  <last_update_submitted>December 13, 2022</last_update_submitted>
  <last_update_submitted_qc>December 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03020160/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03020160/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 7 patients were screened and enrolled in the PK run-in cohort of the study. For the expansion cohort, a total of 44 patients were screened, 41 of whom were enrolled.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Emicizumab: PK Run-In Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
        <group group_id="P2">
          <title>Emicizumab: Expansion Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed 24 Weeks in the Study</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Emicizumab Dose Was Up-Titrated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Opted for a Change in Emicizumab Dosing Regimen</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Emicizumab: PK Run-In Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
        <group group_id="B2">
          <title>Emicizumab: Expansion Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants with 0, 1, or &gt;1 Target Joints in the Last 24 Weeks Prior to Study Entry</title>
          <description>A target joint was defined as a a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0 Target Joints</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1 Target Joint</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;1 Target Joints</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants by Hemophilia A Severity at Baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Mild</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Severe</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Participants by Factor VIII Inhibitor Status at Baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Factor VIII Inhibitor Positive</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Factor VIII Inhibitor Negative</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Bleeds</title>
        <description>The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a &quot;treated bleed&quot; if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a &quot;treatment for bleed&quot;, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.</description>
        <time_frame>From Baseline to at least 24 weeks</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Bleeds</title>
          <description>The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a &quot;treated bleed&quot; if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a &quot;treatment for bleed&quot;, irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>treated bleed rate per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="1.38" upper_limit="4.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Annualized Bleeding Rate (ABR) for All Bleeds</title>
        <description>The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As &quot;all bleeds&quot; comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the &quot;treated bleeds&quot; outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.</description>
        <time_frame>From Baseline to at least 24 weeks</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Annualized Bleeding Rate (ABR) for All Bleeds</title>
          <description>The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As &quot;all bleeds&quot; comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the &quot;treated bleeds&quot; outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>all bleed rate per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="3.10" upper_limit="6.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds</title>
        <description>The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as &quot;spontaneous&quot; if there is no other known contributing factor such as trauma or procedure/surgery. A &quot;treated spontaneous bleed&quot; is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.</description>
        <time_frame>From Baseline to at least 24 weeks</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds</title>
          <description>The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as &quot;spontaneous&quot; if there is no other known contributing factor such as trauma or procedure/surgery. A &quot;treated spontaneous bleed&quot; is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>treated spontaneous bleed rate per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.27" upper_limit="1.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Joint Bleeds</title>
        <description>The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;joint bleed&quot; is defined as a bleed with type reported as &quot;joint&quot; and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A &quot;treated joint bleed&quot; is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of joint bleeds, excluding bleeds due to surgery/procedure.</description>
        <time_frame>From Baseline to at least 24 weeks</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Joint Bleeds</title>
          <description>The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;joint bleed&quot; is defined as a bleed with type reported as &quot;joint&quot; and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A &quot;treated joint bleed&quot; is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of joint bleeds, excluding bleeds due to surgery/procedure.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>treated joint bleed rate per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="0.82" upper_limit="3.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds</title>
        <description>The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;target joint bleed&quot; is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A &quot;treated target joint bleed&quot; is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.</description>
        <time_frame>From Baseline to at least 24 weeks</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds</title>
          <description>The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A &quot;target joint bleed&quot; is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A &quot;treated target joint bleed&quot; is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>treated target joint bleed rate per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.31" upper_limit="3.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Change From Baseline to Week 25 in the Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score for Adult Participants (≥18 Years of Age)</title>
        <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Change From Baseline to Week 25 in the Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score for Adult Participants (≥18 Years of Age)</title>
          <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
          <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.62" lower_limit="-18.36" upper_limit="-8.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Total Score</title>
        <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Total Score</title>
          <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.</description>
          <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Change From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score for Adult Participants (≥18 Years of Age)</title>
        <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Change From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score for Adult Participants (≥18 Years of Age)</title>
          <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
          <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.14" lower_limit="-22.44" upper_limit="-7.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score</title>
        <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score</title>
          <description>The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a &quot;not applicable&quot; option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.</description>
          <population>The analysis included all adult participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Change From Baseline to Week 25 in the Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Total Score for Adolescent Participants (12-17 Years of Age)</title>
        <description>The Haemo-QoL-SF was developed in a series of age-related questionnaires to measure health-related quality of life (HRQoL) in children and adolescents with hemophilia. The short version for older children containing 35 items was selected for adolescents in this study. Items are rated along five response options: never, rarely, sometimes, often, or all the time. This version covers nine dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia, and treatment). Scale scores range from 0 to 100, with lower scores indicating better HRQoL. Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all adolescent participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Change From Baseline to Week 25 in the Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Total Score for Adolescent Participants (12-17 Years of Age)</title>
          <description>The Haemo-QoL-SF was developed in a series of age-related questionnaires to measure health-related quality of life (HRQoL) in children and adolescents with hemophilia. The short version for older children containing 35 items was selected for adolescents in this study. Items are rated along five response options: never, rarely, sometimes, often, or all the time. This version covers nine dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia, and treatment). Scale scores range from 0 to 100, with lower scores indicating better HRQoL. Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.</description>
          <population>The analysis included all adolescent participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.10" spread="6.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Change From Baseline to Week 25 in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score</title>
        <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Change From Baseline to Week 25 in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score</title>
          <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.53" lower_limit="1.15" upper_limit="9.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire VAS Score</title>
        <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire VAS Score</title>
          <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Change From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</title>
        <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Change From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</title>
          <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="0.03" upper_limit="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</title>
        <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
        <time_frame>Baseline, Week 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score</title>
          <description>The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study. The number analyzed represents participants who completed the questionnaire at Baseline and Week 25.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Proportion of Days Away From Work to Expected Days at Work in the Previous Four Weeks</title>
        <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from work (i.e., days of work missed) and the expected number of days at work in the previous four weeks, which is reported here for each time point as the proportion of the number of days away from work to the expected number of days at work.</description>
        <time_frame>Predose at Baseline, Weeks 13 and 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study who were working and completed the questionnaire at Baseline, Week 13, and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Proportion of Days Away From Work to Expected Days at Work in the Previous Four Weeks</title>
          <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from work (i.e., days of work missed) and the expected number of days at work in the previous four weeks, which is reported here for each time point as the proportion of the number of days away from work to the expected number of days at work.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study who were working and completed the questionnaire at Baseline, Week 13, and Week 25.</population>
          <units>away/expected work days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" lower_limit="0.01" upper_limit="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" lower_limit="0.00" upper_limit="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Proportion of Days Away From School to Expected Days at School in the Previous Four Weeks</title>
        <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from school (i.e., days of school missed) and the expected number of days at school in the previous four weeks, which is reported here as the proportion of the number of days away from school to the expected number of days at school.</description>
        <time_frame>Predose at Baseline, Weeks 13 and 25</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study who were enrolled in school and completed the questionnaire at Baseline, Week 13, and Week 25.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Proportion of Days Away From School to Expected Days at School in the Previous Four Weeks</title>
          <description>Participants enrolled in the expansion part of the study reported at each time point the number of days away from school (i.e., days of school missed) and the expected number of days at school in the previous four weeks, which is reported here as the proportion of the number of days away from school to the expected number of days at school.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study who were enrolled in school and completed the questionnaire at Baseline, Week 13, and Week 25.</population>
          <units>away/expected school days</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" lower_limit="0.01" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03" lower_limit="0.00" upper_limit="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Number of Days Hospitalized</title>
        <time_frame>From Baseline until at least 24 weeks of treatment (median [min-max] observation time: 25.57 [24.1-29.4] weeks)</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Number of Days Hospitalized</title>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Percentage of Participants Who Preferred Either the New Emicizumab Subcutaneous (SC) Treatment or Their Previous Hemophilia Intravenous (IV) Treatment, or Had No Preference, as Assessed Using the Emicizumab Preference Survey</title>
        <description>The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with intravenous (IV) factor VIIII (FVIII) or subcutaneous (SC) emicizumab, or no preference.</description>
        <time_frame>Predose at Week 17</time_frame>
        <population>The analysis included all participants enrolled in the expansion part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Percentage of Participants Who Preferred Either the New Emicizumab Subcutaneous (SC) Treatment or Their Previous Hemophilia Intravenous (IV) Treatment, or Had No Preference, as Assessed Using the Emicizumab Preference Survey</title>
          <description>The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with intravenous (IV) factor VIIII (FVIII) or subcutaneous (SC) emicizumab, or no preference.</description>
          <population>The analysis included all participants enrolled in the expansion part of the study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Prefer the New Emicizumab SC Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="91.40" upper_limit="100.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prefer My Old Hemophilia Treatment (IV)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="8.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Have No Preference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="8.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab</title>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
          <units>day</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.95" lower_limit="3.99" upper_limit="7.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.98" lower_limit="6.90" upper_limit="14.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab</title>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
          <units>μg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.8" spread="19.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.7" spread="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of Emicizumab</title>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of Emicizumab</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
          <units>day*μg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="663" spread="19.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1420" spread="20.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Emicizumab</title>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study. t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule; hence, dependent PK parameters, such as AUC[0-inf], could not be estimated after the sixth dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Emicizumab</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study. t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule; hence, dependent PK parameters, such as AUC[0-inf], could not be estimated after the sixth dose of emicizumab.</population>
          <units>day*μg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1490" spread="27.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Apparent Plasma Terminal Half-Life (t1/2) of Emicizumab</title>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study. t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule; hence, t1/2 could not be determined after the sixth dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Apparent Plasma Terminal Half-Life (t1/2) of Emicizumab</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study. t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule; hence, t1/2 could not be determined after the sixth dose of emicizumab.</population>
          <units>day</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.5" spread="38.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab</title>
        <description>Only CL/F is reported after the first dose; the apparent clearance at steady state (CLss/F) is reported after the sixth dose instead. This is because t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule, and dependent PK parameters, such as CL/F, could not be estimated.</description>
        <time_frame>Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab</title>
          <description>Only CL/F is reported after the first dose; the apparent clearance at steady state (CLss/F) is reported after the sixth dose instead. This is because t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule, and dependent PK parameters, such as CL/F, could not be estimated.</description>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study.</population>
          <units>mL/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>After First Dose (Weeks 1-5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.7" spread="23.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>After Sixth Dose (Weeks 21-25)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="20.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Run-In Part: Plasma Concentration of Emicizumab at Specified Timepoints</title>
        <time_frame>Week 1 Day 1 predose and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 6, 7, 8, 9, 11, 13, 15, 17, 19, 21, 22, 23, 24, and 25, and every 12 weeks thereafter to Week 265</time_frame>
        <population>The analysis included all participants enrolled in the PK Run-In part of the study. The number analyzed represents the number of participants with an evaluable sample at a given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>PK Run-In Part: Plasma Concentration of Emicizumab at Specified Timepoints</title>
          <population>The analysis included all participants enrolled in the PK Run-In part of the study. The number analyzed represents the number of participants with an evaluable sample at a given time point.</population>
          <units>μg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1, Day 1 - Predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Concentration could not be estimated because samples were below the lower limit of quantification (BLQ).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 1, Day 1 - 8 hours</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" spread="71.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 1, Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.6" spread="51.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 1, Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.5" spread="29.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2, Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.4" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2, Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.7" spread="21.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3, Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3" spread="20.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3, Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.1" spread="21.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.0" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4, Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.6" spread="15.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.1" spread="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.4" spread="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.2" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.9" spread="20.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.6" spread="24.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.0" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 17</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.7" spread="16.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.8" spread="32.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.5" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.2" spread="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 23</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.5" spread="19.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.9" spread="28.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.2" spread="25.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 37</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.0" spread="15.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 49</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.7" spread="23.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 61</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.1" spread="25.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 73</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.7" spread="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 85</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.0" spread="29.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 97</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.6" spread="17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 109</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.7" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 121</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.6" spread="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 133</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.5" spread="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 145</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34.8" spread="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 157</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.0" spread="20.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 181</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.4" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 193</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.9" spread="21.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 205</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.4" spread="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 217</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.3" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 229</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.1" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 241</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.6" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 253</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.4" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 265</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.4" spread="16.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Expansion Part: Plasma Concentration of Emicizumab at Specified Timepoints</title>
        <time_frame>Predose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 37, 49, 61, 73. 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, and 253</time_frame>
        <population>The analysis included all participants enrolled in the Expansion part of the study. The number analyzed represents the number of participants with an evaluable sample at a given time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Plasma Concentration of Emicizumab at Specified Timepoints</title>
          <population>The analysis included all participants enrolled in the Expansion part of the study. The number analyzed represents the number of participants with an evaluable sample at a given time point.</population>
          <units>μg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Concentration could not be estimated because samples were below the lower limit of quantification (BLQ).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="36.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.8" spread="30.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.3" spread="32.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.8" spread="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.4" spread="45.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.9" spread="49.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 17</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.1" spread="53.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.4" spread="48.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.6" spread="52.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 37</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.6" spread="49.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 49</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.2" spread="48.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 61</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.7" spread="51.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 73</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.1" spread="51.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 85</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="26"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.4" spread="50.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 97</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6" spread="49.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 109</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.0" spread="63.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 121</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.5" spread="60.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 133</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.7" spread="49.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 145</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.5" spread="51.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 157</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="36.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 169</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.7" spread="41.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 181</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.1" spread="47.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 193</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.6" spread="47.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 205</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" spread="48.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 217</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.9" spread="47.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 229</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.2" spread="43.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 241</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.2" spread="46.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 253</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.8" spread="46.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Adverse Event</title>
        <description>The number of participants experiencing at least one adverse event (AE), including all non-serious and serious AEs, is reported here. According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Adverse Event</title>
          <description>The number of participants experiencing at least one adverse event (AE), including all non-serious and serious AEs, is reported here. According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any Adverse Event (AE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Grade ≥3 Adverse Event</title>
        <description>The World Health Organization (WHO) Toxicity Grading Scale was used for assessing adverse event (AE) severity. For AEs that are not specifically listed in the WHO Toxicity Grading Scale, a Grade 3 AE is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a Grade 4 AE is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE; the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Grade ≥3 Adverse Event</title>
          <description>The World Health Organization (WHO) Toxicity Grading Scale was used for assessing adverse event (AE) severity. For AEs that are not specifically listed in the WHO Toxicity Grading Scale, a Grade 3 AE is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a Grade 4 AE is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE; the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment</title>
        <description>According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment</title>
          <description>According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms &quot;severe&quot; and &quot;serious&quot; are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Adverse Event Related to Study Treatment</title>
        <description>According to the ICH guideline for Good Clinical Practice, an adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. In order to assess the causality of an AE, investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE is considered to be related to the study drug, indicating &quot;yes&quot; or &quot;no&quot; accordingly.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Adverse Event Related to Study Treatment</title>
          <description>According to the ICH guideline for Good Clinical Practice, an adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. In order to assess the causality of an AE, investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE is considered to be related to the study drug, indicating &quot;yes&quot; or &quot;no&quot; accordingly.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any Adverse Event Related to Study Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection Site Reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chills</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Presyncope</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythema</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Incorrect Dose Administered</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Accidental Overdose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Iron Deficiency Anaemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs</title>
        <description>The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs</title>
          <description>The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pyrexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tachycardia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings</title>
        <description>Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings</title>
          <description>Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Shift in Clinical Laboratory Parameters From Baseline World Health Organization (WHO) Toxicity Scale Grade 0-2 to Post-Baseline WHO Grade 3 or 4</title>
        <description>An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. In this study, any laboratory value changes were transient and returned to baseline for all participants.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Shift in Clinical Laboratory Parameters From Baseline World Health Organization (WHO) Toxicity Scale Grade 0-2 to Post-Baseline WHO Grade 3 or 4</title>
          <description>An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. In this study, any laboratory value changes were transient and returned to baseline for all participants.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Aspartate Aminotransferase (AST) - High</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium, Corrected - Low</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phosphorus - Low</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium - High</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Local Injection-Site Reaction</title>
        <description>Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an &quot;injection-site reaction&quot; on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a &quot;local injection-site reaction.&quot;</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Local Injection-Site Reaction</title>
          <description>Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an &quot;injection-site reaction&quot; on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a &quot;local injection-site reaction.&quot;</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Thromboembolic Event</title>
        <description>Hypercoagulation and thromboembolic events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers educated patients/caregivers to recognize the signs and symptoms of potential thromboembolism (i.e., dyspnea, chest pain, leg pain or swelling, etc.) and to ensure that they understood the importance of seeking appropriate medical attention.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Thromboembolic Event</title>
          <description>Hypercoagulation and thromboembolic events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers educated patients/caregivers to recognize the signs and symptoms of potential thromboembolism (i.e., dyspnea, chest pain, leg pain or swelling, etc.) and to ensure that they understood the importance of seeking appropriate medical attention.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Thrombotic Microangiopathy</title>
        <description>Thrombotic microangiopathy is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, or central nervous system, etc. Thrombotic microangiopathy events were to be reported as serious adverse events or adverse events of special interest.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Thrombotic Microangiopathy</title>
          <description>Thrombotic microangiopathy is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, or central nervous system, etc. Thrombotic microangiopathy events were to be reported as serious adverse events or adverse events of special interest.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction</title>
        <description>Since emicizumab is a biological product, acute, systemic hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. These events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers (HCP) instructed patients and caregivers how to recognize the signs and symptoms of hypersensitivity, anaphylactic, and anaphylactoid reactions and to contact an HCP or seek emergency care in case of any such occurrence.</description>
        <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction</title>
          <description>Since emicizumab is a biological product, acute, systemic hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. These events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers (HCP) instructed patients and caregivers how to recognize the signs and symptoms of hypersensitivity, anaphylactic, and anaphylactoid reactions and to contact an HCP or seek emergency care in case of any such occurrence.</description>
          <population>The analysis included all participants who received at least one dose of emicizumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-Drug Antibodies to Emicizumab at Any Time Post-Baseline During the Study</title>
        <description>A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) to emicizumab in blood plasma samples. Participants were considered ADA-positive if they were ADA-negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ADA response).</description>
        <time_frame>Baseline, Weeks 5, 9, 13, 17, 21, and 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who received at least one dose of emicizumab. The number analyzed indicates those with both baseline and post-baseline assessments.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Drug Antibodies to Emicizumab at Any Time Post-Baseline During the Study</title>
          <description>A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) to emicizumab in blood plasma samples. Participants were considered ADA-positive if they were ADA-negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ADA response).</description>
          <population>The analysis included all participants who received at least one dose of emicizumab. The number analyzed indicates those with both baseline and post-baseline assessments.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With De Novo Development of Anti-Factor VIII (FVIII) Antibodies</title>
        <description>The levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold.</description>
        <time_frame>Baseline, Weeks 9 and 17 (for non-inhibitor subjects only), Week 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)</time_frame>
        <population>The analysis included all participants who were FVIII inhibitor-negative at baseline and had received at least one dose of emicizumab during the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: PK Run-In Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
          <group group_id="O2">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With De Novo Development of Anti-Factor VIII (FVIII) Antibodies</title>
          <description>The levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold.</description>
          <population>The analysis included all participants who were FVIII inhibitor-negative at baseline and had received at least one dose of emicizumab during the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
        <description>The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
        <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
          <description>The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
          <units>bleeds per year</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treated Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="1.22" upper_limit="3.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>All Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" lower_limit="1.97" upper_limit="4.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Spontaneous Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0.26" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0.69" upper_limit="2.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Target Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0.24" upper_limit="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
        <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
        <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
          <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
          <units>bleeds per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treated Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.25" upper_limit="7.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>All Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="0.63" upper_limit="8.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Spontaneous Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" lower_limit="0.00" upper_limit="4.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="0.07" upper_limit="6.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Target Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.00" upper_limit="4.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
        <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
        <time_frame>From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds</title>
          <description>The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study.</population>
          <units>bleeds per year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Treated Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.20" upper_limit="2.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>All Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0.60" upper_limit="3.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Spontaneous Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" lower_limit="0.00" upper_limit="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treated Target Joint Bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>Treated bleeds per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" lower_limit="0.35" upper_limit="7.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" lower_limit="0.43" upper_limit="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="0.11" upper_limit="6.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="0.23" upper_limit="7.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="0.06" upper_limit="6.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="0.48" upper_limit="8.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.04" upper_limit="5.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" lower_limit="0.10" upper_limit="6.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.23" upper_limit="7.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" lower_limit="0.08" upper_limit="6.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="0.18" upper_limit="6.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.02" upper_limit="5.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="0.13" upper_limit="6.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.23" upper_limit="7.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" lower_limit="0.26" upper_limit="7.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" lower_limit="0.07" upper_limit="6.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="0.15" upper_limit="6.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" lower_limit="0.10" upper_limit="6.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0.05" upper_limit="5.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.02" upper_limit="5.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.40" upper_limit="7.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" lower_limit="0.46" upper_limit="8.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>Treated bleeds per year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="2.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>All bleeds per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" lower_limit="1.67" upper_limit="11.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" lower_limit="1.11" upper_limit="10.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" lower_limit="0.66" upper_limit="8.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" lower_limit="0.42" upper_limit="8.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="0.30" upper_limit="7.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="0.85" upper_limit="9.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="0.17" upper_limit="6.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.24" upper_limit="7.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.37" upper_limit="7.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="0.13" upper_limit="6.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="0.30" upper_limit="7.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="0.05" upper_limit="5.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.23" upper_limit="7.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="0.23" upper_limit="7.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.3" lower_limit="0.33" upper_limit="7.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="0.17" upper_limit="6.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="0.22" upper_limit="7.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" lower_limit="0.10" upper_limit="6.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="0.15" upper_limit="6.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.02" upper_limit="5.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" lower_limit="0.40" upper_limit="7.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" lower_limit="0.46" upper_limit="8.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>All bleeds per year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="8.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="2.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.3" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>Treated spontaneous bleeds per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.00" upper_limit="4.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.02" upper_limit="5.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="0.00" upper_limit="3.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" lower_limit="0.00" upper_limit="4.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="0.00" upper_limit="4.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="0.00" upper_limit="3.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="0.00" upper_limit="4.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.00" upper_limit="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.00" upper_limit="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.00" upper_limit="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.02" upper_limit="5.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="0.18" upper_limit="6.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" lower_limit="0.01" upper_limit="5.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0.00" upper_limit="4.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="0.00" upper_limit="4.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" lower_limit="0.01" upper_limit="5.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0" upper_limit="3.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</title>
        <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
        <time_frame>1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks</time_frame>
        <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
        <group_list>
          <group group_id="O1">
            <title>Emicizumab: Expansion Cohort</title>
            <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time</title>
          <description>The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.</description>
          <population>The analysis includes all participants in the Expansion Cohort who received emicizumab on the study. The number analyzed includes participants with available data over each interval.</population>
          <units>Treated spontaneous bleeds per year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>1 to 12 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>13 to 24 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>25 to 36 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>37 to 48 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>49 to 60 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>61 to 72 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>73 to 84 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>85 to 96 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>97 to 108 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>109 to 120 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>121 to 132 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>133 to 144 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>145 to 156 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>157 to 168 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>169 to 180 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>181 to 192 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>193 to 204 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>205 to 216 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>217 to 228 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>229 to 240 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>241 to 252 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>253 to 264 Weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="0.00" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Emicizumab: PK Run-In Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks (Q4W), with no loading dose, for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
        <group group_id="E2">
          <title>Emicizumab: Expansion Cohort</title>
          <description>Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks (Q4W) for at least 24 weeks. Upon implementation of protocol version 5 (20-Dec-2019), each participant was given the option to choose a preferred emicizumab dosing regimen among those permitted (i.e., emicizumab SC 1.5 mg/kg once every week [QW], 3 mg/kg once every 2 weeks [Q2W], or 6 mg/kg Q4W) and continue on that dosing regimen until discontinuation from the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 25.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>CHOLELITHIASIS OBSTRUCTIVE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>CELLULITIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>HEAD INJURY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>RHABDOMYOLYSIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>BLADDER NEOPLASM</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>DIFFUSE LARGE B-CELL LYMPHOMA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TUMOUR COMPRESSION</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>DEVICE LOOSENING</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>NEPHROLITHIASIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HAEMORRHAGE</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 25.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>IRON DEFICIENCY ANAEMIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>ECZEMA EYELIDS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>DYSPEPSIA</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>ODYNOPHAGIA</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>CHEST PAIN</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>COMPLICATION ASSOCIATED WITH DEVICE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INFLAMMATION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INJECTION SITE REACTION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="40" subjects_affected="9" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>MEDICAL DEVICE DISCOMFORT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>SEASONAL ALLERGY</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>DEVICE RELATED INFECTION</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>EAR INFECTION</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="17" subjects_affected="14" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>PHARYNGITIS</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>SUBCUTANEOUS ABSCESS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TINEA CAPITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>CONTUSION</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>GINGIVAL INJURY</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>HEAD INJURY</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>JOINT INJURY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>LIGAMENT SPRAIN</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>LIMB INJURY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>POST PROCEDURAL INFLAMMATION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TONGUE INJURY</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERCHOLESTEROLAEMIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>VITAMIN D DEFICIENCY</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" events="18" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="43" subjects_affected="17" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>ARTHRITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>EXOSTOSIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>GREATER TROCHANTERIC PAIN SYNDROME</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>JOINT CONTRACTURE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>JOINT LOCK</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL CHEST PAIN</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>NECK PAIN</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>OSTEOARTHRITIS</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>SPINAL OSTEOARTHRITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>SYNOVITIS</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TEMPOROMANDIBULAR JOINT SYNDROME</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>TENDON DISORDER</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="17" subjects_affected="12" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>MOTOR DYSFUNCTION</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>DEVICE BREAKAGE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800-821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03020160
org study id: BO39182
secondary id: 2016-001094-33
nct id: NCT03020160
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This multicenter, open-label, non-randomized study will assess the efficacy, safety,
      pharmacokinetics, and pharmacodynamics of emicizumab administered at a dose of 6 milligrams
      per kilogram (mg/kg) every 4 weeks in participants with hemophilia A with or without
      inhibitors against factor VIII (FVIII). The study consists of 2 parts: a pharmacokinetic (PK)
      run-in part followed by an expansion part.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Expansion Part: Annualized Bleeding Rate (ABR) for Treated Bleeds
time frame: From Baseline to at least 24 weeks
description: The number of treated bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times. A bleed is considered a "treated bleed" if it is directly followed (i.e., no intervening bleed) by a hemophilia medication reported to be a "treatment for bleed", irrespective of time between treatment and the preceding bleed. A bleed and the first treatment thereafter and before a new bleed starts, are considered to be pairs, with the following exception: if multiple bleeds occur on the same calendar day, the subsequent treatment is considered to apply for each of these multiple bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure are excluded.
measure: Expansion Part: Annualized Bleeding Rate (ABR) for All Bleeds
time frame: From Baseline to at least 24 weeks
description: The number of all bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule was implemented exactly as defined for the "treated bleeds" outcome measure. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
measure: Expansion Part: Annualized Bleeding Rate (ABR) for Treated Spontaneous Bleeds
time frame: From Baseline to at least 24 weeks
description: The number of treated spontaneous bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A bleed is classified as "spontaneous" if there is no other known contributing factor such as trauma or procedure/surgery. A "treated spontaneous bleed" is a spontaneous bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of spontaneous bleeds. Bleeds due to surgery/procedure are excluded.
measure: Expansion Part: Annualized Bleeding Rate (ABR) for Treated Joint Bleeds
time frame: From Baseline to at least 24 weeks
description: The number of treated joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "joint bleed" is defined as a bleed with type reported as "joint" and with at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline. A "treated joint bleed" is a joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Treated bleeds that fulfilled the 72-hour rule were included in the analysis of joint bleeds, excluding bleeds due to surgery/procedure.
measure: Expansion Part: Annualized Bleeding Rate (ABR) for Treated Target Joint Bleeds
time frame: From Baseline to at least 24 weeks
description: The number of treated target joint bleeds over the efficacy period is presented as an annualized bleeding rate (ABR) that was analyzed using a negative binomial regression model with efficacy period as an offset to account for the difference in follow-up times (i.e., the time that each participant stays in the study). A "target joint bleed" is defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry. A "treated target joint bleed" is a target joint bleed that also fulfills the conditions of a treated bleed (see ABR for Treated Bleeds for the definition). Bleeds due to surgery/procedure are excluded.
measure: Expansion Part: Change From Baseline to Week 25 in the Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Total Score for Adult Participants (≥18 Years of Age)
time frame: Baseline, Week 25
description: The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.
measure: Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Total Score
time frame: Baseline, Week 25
description: The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 7 points or more on the Total Score was defined as the threshold for a clinically meaningful improvement.
measure: Expansion Part: Change From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score for Adult Participants (≥18 Years of Age)
time frame: Baseline, Week 25
description: The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.
measure: Expansion Part: Percentage of Adult Participants (≥18 Years of Age) With a Clinically Meaningful Improvement From Baseline to Week 25 in the Haem-A-QoL Questionnaire Physical Health Score
time frame: Baseline, Week 25
description: The Haem-A-QoL is a patient-reported questionnaire that was designed for adult participants with hemophilia. It consists of 46 items comprising 10 dimensions (physical health, sports and leisure, school and work, dealing with hemophilia, family planning, feelings, relationships, treatment, view of yourself, and outlook for the future) and a scale representing Total Score. Items are rated along five response options: never, rarely, sometimes, often, or all the time; although for some items there is also a "not applicable" option. Scale scores range from 0 to 100 with lower scores reflective of better quality of life. A decrease of 10 points or more on the Physical Health Score was defined as the threshold for a clinically meaningful improvement.
measure: Expansion Part: Change From Baseline to Week 25 in the Hemophilia-Quality of Life-Short Form (Haemo-QoL-SF) Questionnaire Total Score for Adolescent Participants (12-17 Years of Age)
time frame: Baseline, Week 25
description: The Haemo-QoL-SF was developed in a series of age-related questionnaires to measure health-related quality of life (HRQoL) in children and adolescents with hemophilia. The short version for older children containing 35 items was selected for adolescents in this study. Items are rated along five response options: never, rarely, sometimes, often, or all the time. This version covers nine dimensions considered relevant for the children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports and school, dealing with hemophilia, and treatment). Scale scores range from 0 to 100, with lower scores indicating better HRQoL. Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.
measure: Expansion Part: Change From Baseline to Week 25 in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Visual Analogue Scale (VAS) Score
time frame: Baseline, Week 25
description: The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.
measure: Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire VAS Score
time frame: Baseline, Week 25
description: The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. An increase in the VAS score of 7 points or greater was defined as the threshold for a meaningful improvement.
measure: Expansion Part: Change From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score
time frame: Baseline, Week 25
description: The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.
measure: Expansion Part: Percentage of Participants With a Meaningful Improvement From Baseline to Week 25 in the EQ-5D-5L Questionnaire Index Utility Score
time frame: Baseline, Week 25
description: The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single summary score for the Index Utility Score where overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. An increase in the Index Utility Score of 0.07 points or greater was defined as the threshold for a meaningful improvement.
measure: Expansion Part: Proportion of Days Away From Work to Expected Days at Work in the Previous Four Weeks
time frame: Predose at Baseline, Weeks 13 and 25
description: Participants enrolled in the expansion part of the study reported at each time point the number of days away from work (i.e., days of work missed) and the expected number of days at work in the previous four weeks, which is reported here for each time point as the proportion of the number of days away from work to the expected number of days at work.
measure: Expansion Part: Proportion of Days Away From School to Expected Days at School in the Previous Four Weeks
time frame: Predose at Baseline, Weeks 13 and 25
description: Participants enrolled in the expansion part of the study reported at each time point the number of days away from school (i.e., days of school missed) and the expected number of days at school in the previous four weeks, which is reported here as the proportion of the number of days away from school to the expected number of days at school.
measure: Expansion Part: Number of Days Hospitalized
time frame: From Baseline until at least 24 weeks of treatment (median [min-max] observation time: 25.57 [24.1-29.4] weeks)
measure: Expansion Part: Percentage of Participants Who Preferred Either the New Emicizumab Subcutaneous (SC) Treatment or Their Previous Hemophilia Intravenous (IV) Treatment, or Had No Preference, as Assessed Using the Emicizumab Preference Survey
time frame: Predose at Week 17
description: The Emicizumab Preference Survey is a fit-for-purpose questionnaire developed by the sponsor to record the participant's preference for treatment with intravenous (IV) factor VIIII (FVIII) or subcutaneous (SC) emicizumab, or no preference.
measure: PK Run-In Part: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
measure: PK Run-In Part: Maximum Observed Plasma Concentration (Cmax) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
measure: PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
measure: PK Run-In Part: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
measure: PK Run-In Part: Apparent Plasma Terminal Half-Life (t1/2) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
measure: PK Run-In Part: Apparent Clearance (CL/F) of Emicizumab
time frame: Week 1 Day 1 predose (0 hours) and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 21, 22, 23, 24, and 25
description: Only CL/F is reported after the first dose; the apparent clearance at steady state (CLss/F) is reported after the sixth dose instead. This is because t1/2 was not properly estimated after the first dose due to sampling time and dosing schedule, and dependent PK parameters, such as CL/F, could not be estimated.
measure: PK Run-In Part: Plasma Concentration of Emicizumab at Specified Timepoints
time frame: Week 1 Day 1 predose and 8 hours postdose, and Week 1 Days 3 and 5, Week 2 Days 8 and 11, Week 3 Days 15 and 18, Week 4 Days 22 and 25, and Day 1 of Weeks 5, 6, 7, 8, 9, 11, 13, 15, 17, 19, 21, 22, 23, 24, and 25, and every 12 weeks thereafter to Week 265
measure: Expansion Part: Plasma Concentration of Emicizumab at Specified Timepoints
time frame: Predose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 37, 49, 61, 73. 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 217, 229, 241, and 253
measure: Number of Participants With at Least One Adverse Event
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: The number of participants experiencing at least one adverse event (AE), including all non-serious and serious AEs, is reported here. According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms "severe" and "serious" are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.
measure: Number of Participants With at Least One Grade ≥3 Adverse Event
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: The World Health Organization (WHO) Toxicity Grading Scale was used for assessing adverse event (AE) severity. For AEs that are not specifically listed in the WHO Toxicity Grading Scale, a Grade 3 AE is defined as: severe, marked limitation in activity, some assistance usually required, medical intervention or therapy required, hospitalization possible; and a Grade 4 AE is defined as: life-threatening, extreme limitation in activity, significant assistance required, significant medical intervention or therapy required, hospitalization or hospice care probable. The terms "severe" and "serious" are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE; the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.
measure: Number of Participants With at Least One Adverse Event Leading to Withdrawal From Treatment
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: According to the ICH guideline for Good Clinical Practice, an AE is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms "severe" and "serious" are not synonymous. A serious AE is any AE that is a significant medical event meeting any of the standard criteria. Severity refers to the intensity of an AE (e.g., rated as mild, moderate, or severe, or according to the World Health Organization [WHO] toxicity grading scale); the event itself may be of relatively minor medical significance. Severity and seriousness were independently assessed by the investigator for each reported AE.
measure: Number of Participants With at Least One Adverse Event Related to Study Treatment
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: According to the ICH guideline for Good Clinical Practice, an adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. In order to assess the causality of an AE, investigators used their knowledge of the patient, the circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an AE is considered to be related to the study drug, indicating "yes" or "no" accordingly.
measure: Number of Participants With at Least One Adverse Event of Changes From Baseline in Vital Signs
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab.
measure: Number of Participants With at Least One Adverse Event of Changes From Baseline in Physical Examination Findings
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: Post-baseline physical examination abnormalities that were not present at baseline or worsened were reported as adverse events.
measure: Number of Participants With at Least One Shift in Clinical Laboratory Parameters From Baseline World Health Organization (WHO) Toxicity Scale Grade 0-2 to Post-Baseline WHO Grade 3 or 4
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. In this study, any laboratory value changes were transient and returned to baseline for all participants.
measure: Number of Participants With at Least One Local Injection-Site Reaction
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: Local adverse events that occurred within 24 hours after study drug administration and, in the investigator's opinion, were judged to be related to study drug injection, were captured as an "injection-site reaction" on the Adverse Event electronic Case Report Form (eCRF). An injection-related reaction that was localized was marked as a "local injection-site reaction."
measure: Number of Participants With at Least One Thromboembolic Event
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: Hypercoagulation and thromboembolic events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers educated patients/caregivers to recognize the signs and symptoms of potential thromboembolism (i.e., dyspnea, chest pain, leg pain or swelling, etc.) and to ensure that they understood the importance of seeking appropriate medical attention.
measure: Number of Participants With at Least One Thrombotic Microangiopathy
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: Thrombotic microangiopathy is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, or central nervous system, etc. Thrombotic microangiopathy events were to be reported as serious adverse events or adverse events of special interest.
measure: Number of Participants With at Least One Systemic Hypersensitivity, Anaphylaxis, or Anaphylactoid Reaction
time frame: From Baseline to study completion, dose up-titration, or change of dosing regimen, whichever occurred first (up to 5 years, 5 months)
description: Since emicizumab is a biological product, acute, systemic hypersensitivity reactions, including anaphylaxis and anaphylactic reactions, may occur. These events were to be reported as serious adverse events or adverse events of special interest. Healthcare providers (HCP) instructed patients and caregivers how to recognize the signs and symptoms of hypersensitivity, anaphylactic, and anaphylactoid reactions and to contact an HCP or seek emergency care in case of any such occurrence.
measure: Number of Participants With Anti-Drug Antibodies to Emicizumab at Any Time Post-Baseline During the Study
time frame: Baseline, Weeks 5, 9, 13, 17, 21, and 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)
description: A validated enzyme-linked immunosorbent assay (ELISA) method was used to analyze the levels of anti-drug antibodies (ADAs) to emicizumab in blood plasma samples. Participants were considered ADA-positive if they were ADA-negative at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ADA response).
measure: Number of Participants With De Novo Development of Anti-Factor VIII (FVIII) Antibodies
time frame: Baseline, Weeks 9 and 17 (for non-inhibitor subjects only), Week 25, and every 12 weeks thereafter until study completion (up to 5 years, 5 months)
description: The levels of anti-FVIII antibodies (inhibitors) were analyzed using a validated FVIII activity assay. A participant was considered to have developed de novo FVIII inhibitors if the inhibitor levels detected in a post-baseline sample reached or exceeded a pre-determined threshold.
measure: Long-Term Efficacy of Emicizumab: Model-Based Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds
time frame: From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)
description: The number of bleeds over the efficacy period was assessed as an ABR using a negative binomial (NB) regression model, which accounts for different follow-up times. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.
measure: Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds
time frame: From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)
description: The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.
measure: Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds, All Bleeds, Treated Spontaneous Bleeds, Treated Joint Bleeds, and Treated Target Joint Bleeds
time frame: From start of emicizumab treatment to study completion, dose up-titration, or change of dosing regimen (median [min-max] efficacy period for all emicizumab participants: 191.14 [28.0-264.4] weeks)
description: The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. All bleeds included both treated and non-treated bleeds. Treated spontaneous bleeds: treated bleeds with no known contributing factor (e.g., trauma, surgery). Treated joint bleeds: treated bleeds in a joint associated with unusual sensation (aura) in a joint, in combination with another symptom: swelling/warmth, pain/decreased range of motion (RoM), or difficulty moving the joint. Treated target joint bleeds: treated joint bleeds in a target joint, defined as a joint in which greater than or equal to (≥) 3 treated joint bleeds occurred during the last 24 weeks prior to study entry. For all types of bleeds: the 72-hour rule was implemented, and bleeds due to surgery/procedure and bleeds after up-titration or change of dosing regimen were excluded.
measure: Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
measure: Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of treated bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: a bleed for which coagulation factors were administered. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
measure: Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
measure: Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for All Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of all bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds included both treated bleeds (with coagulation factors) and non-treated bleeds. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
measure: Long-Term Efficacy of Emicizumab: Mean Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
measure: Long-Term Efficacy of Emicizumab: Median Calculated Annualized Bleeding Rates (ABR) for Treated Spontaneous Bleeds Per 12-Week Intervals Over Time
time frame: 1-12, 13-24, 25-36, 37-48, 49-60, 61-72, 73-84, 85-96, 97-108, 109-120, 121-132, 133-144, 145-156, 157-168, 169-180, 181-192, 193-204, 205-216, 217-228, 229-240, 241-252, and 253-264 weeks
description: The number of treated spontaneous bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds were defined as treated (with coagulation factors) bleeds with no known contributing factor (e.g., trauma, surgery). The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded. For participants with dose up-titration or a change in emicizumab dosing regimen (after implementation of protocol v5), the efficacy period ended the day before the first day on the up-titrated dose or changed dosing regimen.
arm group label: Emicizumab: PK Run-in Cohort
arm group type: Experimental
description: Participants received emicizumab subcutaneously (SC) at a dose of 6 mg/kg once every 4 weeks, with no loading dose, for at least 24 weeks.
arm group label: Emicizumab: Expansion Cohort
arm group type: Experimental
description: Participants received emicizumab subcutaneously (SC) at a loading dose of 3 mg/kg once every week for the first 4 weeks followed by a maintenance dose of 6 mg/kg emicizumab SC once every 4 weeks for at least 24 weeks.
intervention type: Drug
intervention name: Emicizumab
description: Emicizumab will be administered according to dose and schedule described in respective arms. After at least 24 weeks on prophylactic emicizumab, individuals who experienced suboptimal bleeding control on emicizumab (according to protocol-defined criteria) had the opportunity to increase their dose to 3 mg/kg weekly. Upon implementation of protocol Version 5 (20-Dec-2019), treatment duration was extended. During this study prolongation, participants had the opportunity to switch to a preferred emicizumab dosing regimen (1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks) in order to provide them the same flexibility as with commercial product.
arm group label: Emicizumab: Expansion Cohort
arm group label: Emicizumab: PK Run-in Cohort
other name: Hemlibra
other name: RO5534262
other name: ACE910
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Australia
country: Belgium
country: Japan
country: Poland
country: Spain
country: United States
country: Germany
responsible party type: Sponsor
mesh term: Hemophilia A
provided document: 
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limitations and caveats: Given the small number of adolescent participants, the results of the Haemo-QoL-SF questionnaire should be interpreted with caution.
point of contact: 