<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/NCT02210091</url>
  </required_header>
  <id_info>
    <org_study_id>261202</org_study_id>
    <secondary_id>2014-000742-30</secondary_id>
    <nct_id>NCT02210091</nct_id>
  </id_info>
  <brief_title>BAX 855 Pediatric Study</brief_title>
  <official_title>A Phase 3 Prospective, Uncontrolled, Multicenter Study Evaluating Pharmacokinetics, Efficacy, Safety, and Immunogenicity of BAX 855 (PEGylated Full-length Recombinant FVIII) in Previously Treated Pediatric Patients With Severe Hemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baxalta now part of Shire</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study purpose is:&#xD;
&#xD;
        -  To assess the incidence of FVIII inhibitory antibodies during 6 months of twice weekly&#xD;
           prophylactic treatment with BAX 855 or 50 exposure days (EDs), whichever occurs last.&#xD;
&#xD;
        -  To compare pharmacokinetic (PK) parameters to ADVATE.&#xD;
&#xD;
        -  To assess hemostatic efficacy in prophylaxis and the treatment of bleeding episodes.&#xD;
&#xD;
        -  To evaluate safety and immunogenicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2014</start_date>
  <completion_date type="Actual">October 23, 2015</completion_date>
  <primary_completion_date type="Actual">October 23, 2015</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
    <description>Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units [BU].</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized Bleeding Rate (ABR)</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
    <description>The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes. The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Number of Infusions Per Bleeding Episode</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode</measure>
    <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
    <description>Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale): Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-serious Adverse Events Possibly or Probably Related to BAX 855</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Changes in Vital Signs</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
    <description>Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
    <description>The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count. The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides. For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins</measure>
    <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
    <description>Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Mean Residence Time (MRT)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Clearance (CL)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Plasma Half-life (T1/2)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Incremental Recovery (IR)</measure>
    <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
    <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay</measure>
    <time_frame>Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)</time_frame>
    <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;One stage clotting assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay</measure>
    <time_frame>Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)</time_frame>
    <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;Chromogenic assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Hemophilia A</condition>
  <arm_group>
    <arm_group_label>&lt;6 years old</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>≥6 to &lt;12 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method</intervention_name>
    <description>Pharmacokinetic (PK) analysis of ADVATE</description>
    <arm_group_label>&lt;6 years old</arm_group_label>
    <arm_group_label>≥6 to &lt;12 years</arm_group_label>
    <other_name>ADVATE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PEGylated Recombinant Factor VIII</intervention_name>
    <description>Pharmacokinetic (PK) analysis of BAX 855</description>
    <arm_group_label>&lt;6 years old</arm_group_label>
    <arm_group_label>≥6 to &lt;12 years</arm_group_label>
    <other_name>BAX 855</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PEGylated Recombinant Factor VIII</intervention_name>
    <description>Prophylaxis treatment</description>
    <arm_group_label>&lt;6 years old</arm_group_label>
    <arm_group_label>≥6 to &lt;12 years</arm_group_label>
    <other_name>BAX 855</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Severe hemophilia A (Factor VIII (FVIII) &lt;1%) determined by central laboratory.&#xD;
&#xD;
          -  &lt;12 years old at the time of screening.&#xD;
&#xD;
          -  Participants aged ≥6 to &lt;12 years of age have been previously treated with&#xD;
             plasma-derived and/or recombinant Factor VIII (rFVIII) concentrate(s) for a minimum of&#xD;
             150 exposure days (EDs) (based on the participant's medical records).&#xD;
&#xD;
          -  Participants &lt;6 years of age have been previously treated with plasma-derived and/or&#xD;
             rFVIII concentrate(s) for at least 50 EDs (based on the participant's medical&#xD;
             records).&#xD;
&#xD;
          -  Participant is human immunodeficiency virus (HIV) negative; or HIV positive with&#xD;
             stable disease and CD4+ count of ≥200 cells/mm^3, as confirmed by central laboratory.&#xD;
&#xD;
          -  Participant and/or legal representative accepts prophylactic treatment over a period&#xD;
             of 6 months.&#xD;
&#xD;
          -  Participant and/or the legal representative is willing and able to comply with the&#xD;
             requirements of the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has detectable FVIII inhibitory antibodies (≥0.4 Bethesda Units (BU) using&#xD;
             the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at&#xD;
             screening.&#xD;
&#xD;
          -  Participant has a history of FVIII inhibitory antibodies (≥0.4 BU using the Nijmegen&#xD;
             modification of the Bethesda assay or ≥0.6 BU using the Bethesda assay) at any time&#xD;
             prior to screening.&#xD;
&#xD;
          -  Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene&#xD;
             glycol (PEG), or Tween 80.&#xD;
&#xD;
          -  Participant has been diagnosed with an inherited or acquired hemostatic defect other&#xD;
             than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).&#xD;
&#xD;
          -  Participant's platelet count is &lt;100,000/μL.&#xD;
&#xD;
          -  Participant has severe chronic hepatic dysfunction (eg, ≥5 times upper limit of normal&#xD;
             (ULN) alanine aminotransferase (ALT), as confirmed by central laboratory at screening,&#xD;
             or a documented international normalized ratio (INR) &gt;1.5).&#xD;
&#xD;
          -  Participant has severe renal impairment (serum creatinine &gt;1.5 times ULN).&#xD;
&#xD;
          -  Participant is scheduled to receive during the course of the study, an&#xD;
             immunomodulating drug (eg, corticosteroid agents at a dose equivalent to&#xD;
             hydrocortisone &gt;10 mg/day, or α-interferon) other than anti-retroviral chemotherapy.&#xD;
&#xD;
          -  Participant has current or recent (&lt;30 days) use of other PEGylated drugs prior to&#xD;
             study participation or is scheduled to use such drugs during study participation.&#xD;
&#xD;
          -  Participant has participated in another clinical study involving an investigational&#xD;
             product (IP) or investigational device within 30 days prior to enrollment or is&#xD;
             scheduled to participate in another clinical study involving an IP or investigational&#xD;
             device during the course of this study.&#xD;
&#xD;
          -  Participant has a medical, psychiatric, or cognitive illness or recreational&#xD;
             drug/alcohol use that, in the opinion of the Investigator, would affect participant&#xD;
             safety or compliance.&#xD;
&#xD;
          -  Participant's legal representative is a member of the team conducting this study or is&#xD;
             in a dependent relationship with one of the study team members. Dependent&#xD;
             relationships include close relatives (ie, children, partner/spouse, siblings,&#xD;
             parents) as well as employees of the investigator or site personnel conducting the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>11 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida College of Medicine</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cornell University</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Hospital-Weill</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Childrens Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationwide Childrens Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAP Sveti Georgi EAD</name>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialized Hospital for Active Treatment of Oncohematological Diseases in Children</name>
      <address>
        <city>Sofia</city>
        <zip>1527</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment &quot;Sveta Marina&quot;</name>
      <address>
        <city>Varna</city>
        <zip>9010</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong</name>
      <address>
        <city>Shatin</city>
        <state>New Territories</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eulji University Hosptial</name>
      <address>
        <city>Seo-gu</city>
        <state>Daejeon</state>
        <zip>302-799</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ulsan University Hosptial</name>
      <address>
        <city>Dong-gu</city>
        <state>Ulsan</state>
        <zip>682-714</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>134-727</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pulau Pinang</name>
      <address>
        <city>George Town</city>
        <state>Penang</state>
        <zip>10450</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Umum Sarawak</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sibu</name>
      <address>
        <city>Sibu</city>
        <state>Sarawak</state>
        <zip>96000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ampang Hospital</name>
      <address>
        <city>Ampang</city>
        <state>Selangor</state>
        <zip>68000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tengku Ampian Rahimah (TAR) Hospital</name>
      <address>
        <city>Klang</city>
        <state>Selangor</state>
        <zip>41200</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Centre</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>460026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung City</city>
        <state>Xitun District</state>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Faculty of Medicine, Department of Pediatric Immunology</name>
      <address>
        <city>Cerrahpasa</city>
        <state>Istanbul</state>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara University Medical Faculty</name>
      <address>
        <city>Ankara</city>
        <zip>06560</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akdeniz Univesity Medical Faculty</name>
      <address>
        <city>Antalya</city>
        <zip>07059</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yuzuncu Yil University Medical Faculty</name>
      <address>
        <city>Van</city>
        <zip>65000</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Blood Pathology and Transfusion Medicine of Academy of Medical Sciences of Ukraine</name>
      <address>
        <city>Lviv</city>
        <zip>79044</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Childrens Hospital NHS Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Thomas's Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital For Children</name>
      <address>
        <city>London</city>
        <zip>WC1N 3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Manchester Children's Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Hong Kong</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Mullins ES, Stasyshyn O, Alvarez-Roman MT, Osman D, Liesner R, Engl W, Sharkhawy M, Abbuehl BE. Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia. 2017 Mar;23(2):238-246. doi: 10.1111/hae.13119. Epub 2016 Nov 27.</citation>
    <PMID>27891721</PMID>
  </results_reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <results_first_submitted>December 2, 2016</results_first_submitted>
  <results_first_submitted_qc>December 2, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 5, 2016</results_first_posted>
  <disposition_first_submitted>October 20, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>October 20, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">October 21, 2016</disposition_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2021</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Factor VIII</mesh_term>
    <mesh_term>BAX 855</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>52 sites participated in this study. 39 study sites enrolled participants and 13 sites were initiated but were inactive.</recruitment_details>
      <pre_assignment_details>73 participants enrolled and were screened for study participation. There were 9 screen failures. Among these, 2 participants were screen failures at first screening but entered the study later. 66 participants were dosed in the prophylactic part of the study, of whom 31 participants were also dosed in the PK part prior to prophylaxis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>&lt;6 Years Old</title>
        </group>
        <group group_id="P2">
          <title>6 to &lt;12 Years Old</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>&lt;6 Years Old</title>
        </group>
        <group group_id="B2">
          <title>6 to &lt;12 Years Old</title>
        </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="32"/>
            <count group_id="B2" value="34"/>
            <count group_id="B3" value="66"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.7" spread="1.17"/>
                    <measurement group_id="B2" value="8.1" spread="1.92"/>
                    <measurement group_id="B3" value="6.0" spread="2.70"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)</title>
        <description>Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units [BU].</description>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>Participants in the BAX 855 Safety Analysis Set who developed an inhibitor at any time plus participants who did not develop an inhibitor, had 50 or more exposure days (EDs) to BAX 855 and had FVIII Inhibitory test results after 50 EDs.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)</title>
          <description>Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units [BU].</description>
          <population>Participants in the BAX 855 Safety Analysis Set who developed an inhibitor at any time plus participants who did not develop an inhibitor, had 50 or more exposure days (EDs) to BAX 855 and had FVIII Inhibitory test results after 50 EDs.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="57"/>
              </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 group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Bleeding Rate (ABR)</title>
        <description>The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes. The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.</description>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>Full Analysis Set: All participants who received at least 1 dose of BAX 855 in either PK or prophylaxis part of study</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.</description>
          </group>
          <group group_id="O3">
            <title>Full Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855 in either the Pharmacokinetic (PK) part of the study or the prophylaxis part of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Bleeding Rate (ABR)</title>
          <description>The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes. The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.</description>
          <population>Full Analysis Set: All participants who received at least 1 dose of BAX 855 in either PK or prophylaxis part of study</population>
          <units>bleeding episodes 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="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall annualized bleeding rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.37" spread="3.508" lower_limit="1.486" upper_limit="3.778"/>
                    <measurement group_id="O2" value="3.75" spread="9.046" lower_limit="2.429" upper_limit="5.781"/>
                    <measurement group_id="O3" value="3.04" spread="6.988" lower_limit="2.208" upper_limit="4.186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Annualized rate of joint bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.862" spread="2.622" lower_limit="0.381" upper_limit="1.946"/>
                    <measurement group_id="O2" value="1.355" spread="2.590" lower_limit="0.648" upper_limit="2.833"/>
                    <measurement group_id="O3" value="1.103" spread="2.597" lower_limit="0.637" upper_limit="1.910"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Annualized rate of target joint bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0.354" lower_limit="0" upper_limit="NA">NA = infinity</measurement>
                    <measurement group_id="O2" value="0" spread="1.146" lower_limit="0" upper_limit="NA">NA = infinity</measurement>
                    <measurement group_id="O3" value="0" spread="0.865" lower_limit="0" upper_limit="NA">NA = infinity</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Annualized rate of non-target joint bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.763" spread="2.618" lower_limit="0.299" upper_limit="1.950"/>
                    <measurement group_id="O2" value="0.998" spread="2.253" lower_limit="0.410" upper_limit="2.430"/>
                    <measurement group_id="O3" value="0.892" spread="2.420" lower_limit="0.466" upper_limit="1.706"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Annualized spontaneous bleeding rate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.018" spread="2.048" lower_limit="0.523" upper_limit="1.978"/>
                    <measurement group_id="O2" value="1.316" spread="2.467" lower_limit="0.710" upper_limit="2.438"/>
                    <measurement group_id="O3" value="1.164" spread="2.260" lower_limit="0.740" upper_limit="1.832"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Annualized rate of injury-related bleeds</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.628" spread="2.308" lower_limit="0.989" upper_limit="2.679"/>
                    <measurement group_id="O2" value="2.586" spread="8.678" lower_limit="1.639" upper_limit="4.080"/>
                    <measurement group_id="O3" value="2.089" spread="6.471" lower_limit="1.492" upper_limit="2.925"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>infusions per month</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.07" spread="0.245"/>
                    <measurement group_id="O2" value="7.72" spread="0.974"/>
                    <measurement group_id="O3" value="7.89" spread="0.736"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>infusions per year</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.82" spread="2.942"/>
                    <measurement group_id="O2" value="92.61" spread="11.693"/>
                    <measurement group_id="O3" value="94.65" spread="8.834"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="458.93" spread="46.161"/>
                    <measurement group_id="O2" value="455.86" spread="76.101"/>
                    <measurement group_id="O3" value="457.35" spread="62.919"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5507.20" spread="553.931"/>
                    <measurement group_id="O2" value="5470.32" spread="913.210"/>
                    <measurement group_id="O3" value="5488.20" spread="755.033"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Number of Infusions Per Bleeding Episode</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Number of Infusions Per Bleeding Episode</title>
          <population>Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.</population>
          <units>infusions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17" spread="0.362"/>
                    <measurement group_id="O2" value="1.40" spread="0.655"/>
                    <measurement group_id="O3" value="1.30" spread="0.551"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode</title>
        <time_frame>During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last</time_frame>
        <population>Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt; 6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode</title>
          <population>Participants in the BAX 855 Safety Analysis Set who had treated bleeding episodes.</population>
          <units>IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="45"/>
                <count group_id="O3" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Average dose to treat bleeding episode</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.21" spread="16.681"/>
                    <measurement group_id="O2" value="62.31" spread="38.764"/>
                    <measurement group_id="O3" value="57.85" spread="31.041"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average dose per infusion per bleeding episode</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.58" spread="10.750"/>
                    <measurement group_id="O2" value="43.76" spread="15.304"/>
                    <measurement group_id="O3" value="44.56" spread="13.327"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed</title>
        <description>Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale): Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.</description>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>Participants in the Full Analysis Set who had treated bleeding episodes.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>Full Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed</title>
          <description>Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale): Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.</description>
          <population>Participants in the Full Analysis Set who had treated bleeding episodes.</population>
          <units>bleeding episodes</units>
          <param>Number</param>
          <units_analyzed>bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="34"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="45"/>
                <count group_id="O3" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Excellent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Good</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="20"/>
                    <measurement group_id="O3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fair</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855</title>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>serious adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Investigator Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sponsor Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Non-serious Adverse Events Possibly or Probably Related to BAX 855</title>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Non-serious Adverse Events Possibly or Probably Related to BAX 855</title>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Investigator Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sponsor Assessment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Changes in Vital Signs</title>
        <description>Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.</description>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Changes in Vital Signs</title>
          <description>Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.</description>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)</title>
        <description>The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count. The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides. For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.</description>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>BAX 855 Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)</title>
          <description>The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count. The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides. For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.</description>
          <population>BAX 855 Safety Analysis Set.</population>
          <units>clinically significant findings</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="34"/>
                <count group_id="O3" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hematology-CS Rise in Eosinophils</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Clin. Chemistry-CS Rise in Alkaline Phosphatase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins</title>
        <description>Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).</description>
        <time_frame>After first exposure to BAX 855 until completion of study - approx. 6 months per participant.</time_frame>
        <population>BAX 855 Safety Analysis Set: Data not available for 1 participant in the 6 to &lt;12 years group as participant was prematurely withdrawn from study.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
            <description>Participants &lt;6 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who received at least one dose of BAX 855.</description>
          </group>
          <group group_id="O3">
            <title>BAX 855 Safety Analysis Set</title>
            <description>Participants who received at least one dose of BAX 855.</description>
          </group>
        </group_list>
        <measure>
          <title>Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins</title>
          <description>Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).</description>
          <population>BAX 855 Safety Analysis Set: Data not available for 1 participant in the 6 to &lt;12 years group as participant was prematurely withdrawn from study.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="32"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Positive binding IgG antibodies to FVIII</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding IgM antibodies to FVIII</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding IgG antibodies to PEG-FVIII</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding IgM antibodies to PEG-FVIII</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding IgG antibodies to PEG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding IgM antibodies to PEG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Positive binding Ig antibodies to CHO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set - &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years olde who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set.</population>
          <units>IU•hr/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14000" spread="3070"/>
                    <measurement group_id="O2" value="14400" spread="1800"/>
                    <measurement group_id="O3" value="14200" spread="2420"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11600" spread="3070"/>
                    <measurement group_id="O2" value="16600" spread="3290"/>
                    <measurement group_id="O3" value="14400" spread="4040"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19500" spread="7580"/>
                    <measurement group_id="O2" value="20100" spread="4930"/>
                    <measurement group_id="O3" value="19800" spread="6160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21900" spread="15900"/>
                    <measurement group_id="O2" value="22600" spread="5140"/>
                    <measurement group_id="O3" value="22300" spread="11200"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)</title>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>The PK parameters were derived using a non-compartmental estimation approach using a flexible sampling design to provide point and interval estimates for summary PK parameter using a batch method. AUC/Dose is not a standard output parameter so this calculation was not done.</population>
        <group_list>
          <group group_id="O1">
            <title>Overall Study Arm</title>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)</title>
          <population>The PK parameters were derived using a non-compartmental estimation approach using a flexible sampling design to provide point and interval estimates for summary PK parameter using a batch method. AUC/Dose is not a standard output parameter so this calculation was not done.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Mean Residence Time (MRT)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set - &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Mean Residence Time (MRT)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>hours (hr)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3" spread="3.95"/>
                    <measurement group_id="O2" value="14.2" spread="2.64"/>
                    <measurement group_id="O3" value="13.8" spread="3.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" spread="2.52"/>
                    <measurement group_id="O2" value="11.6" spread="1.20"/>
                    <measurement group_id="O3" value="12.0" spread="1.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.0" spread="3.51"/>
                    <measurement group_id="O2" value="17.8" spread="2.40"/>
                    <measurement group_id="O3" value="17.5" spread="2.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.7" spread="12.6"/>
                    <measurement group_id="O2" value="17.2" spread="3.72"/>
                    <measurement group_id="O3" value="17.9" spread="8.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Clearance (CL)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set - &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Clearance (CL)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0775" spread="0.0132"/>
                    <measurement group_id="O2" value="0.1250" spread="0.04200"/>
                    <measurement group_id="O3" value="0.1030" spread="0.0398"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0933" spread="0.0106"/>
                    <measurement group_id="O2" value="0.1040" spread="0.00875"/>
                    <measurement group_id="O3" value="0.0994" spread="0.0110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0596" spread="0.0190"/>
                    <measurement group_id="O2" value="0.0913" spread="0.0276"/>
                    <measurement group_id="O3" value="0.0770" spread="0.0286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0574" spread="0.0174"/>
                    <measurement group_id="O2" value="0.0812" spread="0.0248"/>
                    <measurement group_id="O3" value="0.0704" spread="0.0246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Plasma Half-life (T1/2)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set - &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Plasma Half-life (T1/2)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>hours (hr)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.24" spread="2.74"/>
                    <measurement group_id="O2" value="9.82" spread="1.83"/>
                    <measurement group_id="O3" value="9.56" spread="2.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.68" spread="1.75"/>
                    <measurement group_id="O2" value="8.04" spread="0.83"/>
                    <measurement group_id="O3" value="8.33" spread="1.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" spread="2.43"/>
                    <measurement group_id="O2" value="12.4" spread="1.67"/>
                    <measurement group_id="O3" value="12.1" spread="2.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.0" spread="8.74"/>
                    <measurement group_id="O2" value="11.9" spread="2.58"/>
                    <measurement group_id="O3" value="12.4" spread="6.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>litre (L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" spread="0.302"/>
                    <measurement group_id="O2" value="1.69" spread="0.350"/>
                    <measurement group_id="O3" value="1.39" spread="0.470"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.14" spread="0.107"/>
                    <measurement group_id="O2" value="1.20" spread="0.0548"/>
                    <measurement group_id="O3" value="1.18" spread="0.0857"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.97" spread="0.230"/>
                    <measurement group_id="O2" value="1.59" spread="0.343"/>
                    <measurement group_id="O3" value="1.31" spread="0.427"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.907" spread="0.124"/>
                    <measurement group_id="O2" value="1.33" spread="0.233"/>
                    <measurement group_id="O3" value="1.14" spread="0.285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Incremental Recovery (IR)</title>
        <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set - &lt;6 Years Old</title>
            <description>Participants &lt;6 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O2">
            <title>PK Analysis Set - 6 to &lt;12 Years Old</title>
            <description>Participants 6 to &lt;12 years old who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmcokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
          <group group_id="O3">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Incremental Recovery (IR)</title>
          <description>The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>IU/dL : IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="17"/>
                <count group_id="O3" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8563" spread="0.76004"/>
                    <measurement group_id="O2" value="1.8696" spread="0.25856"/>
                    <measurement group_id="O3" value="1.8636" spread="0.53481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - ADVATE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7374" spread="0.29110"/>
                    <measurement group_id="O2" value="2.0458" spread="0.31739"/>
                    <measurement group_id="O3" value="1.9065" spread="0.33879"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>One stage clotting assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8809" spread="0.48894"/>
                    <measurement group_id="O2" value="1.9342" spread="0.47451"/>
                    <measurement group_id="O3" value="1.9101" spread="0.47371"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay - BAX 855</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8813" spread="0.27069"/>
                    <measurement group_id="O2" value="2.1710" spread="0.38472"/>
                    <measurement group_id="O3" value="2.0402" spread="0.36355"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay</title>
        <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;One stage clotting assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
        <time_frame>Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)</time_frame>
        <population>Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
          </group>
          <group group_id="O3">
            <title>Full Analysis Set</title>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay</title>
          <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;One stage clotting assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
          <population>Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6</population>
          <units>IU/dL : IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline [n=15, 16, 31]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6889" spread="0.27610"/>
                    <measurement group_id="O2" value="1.7843" spread="0.35942"/>
                    <measurement group_id="O3" value="1.7381" spread="0.32017"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5 (or after 10-15 EDs) [n= 27, 30, 57]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8952" spread="0.55483"/>
                    <measurement group_id="O2" value="1.8661" spread="0.49785"/>
                    <measurement group_id="O3" value="1.8799" spread="0.52105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 [n= 26, 31, 57]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6818" spread="0.23069"/>
                    <measurement group_id="O2" value="1.9212" spread="0.42496"/>
                    <measurement group_id="O3" value="1.8120" spread="0.36738"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6 (Termination/Completion) [n=27, 28, 55]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5801" spread="0.31568"/>
                    <measurement group_id="O2" value="1.7120" spread="0.36588"/>
                    <measurement group_id="O3" value="1.6472" spread="0.34546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay</title>
        <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;Chromogenic assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
        <time_frame>Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)</time_frame>
        <population>Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6.</population>
        <group_list>
          <group group_id="O1">
            <title>&lt;6 Years Old</title>
          </group>
          <group group_id="O2">
            <title>6 to &lt;12 Years Old</title>
          </group>
          <group group_id="O3">
            <title>Full Analysis Set</title>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay</title>
          <description>Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- &quot;Pharmacokinetics (PK): Incremental Recovery (IR)&quot;, for the category &quot;Chromogenic assay - BAX 855&quot; For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] &lt; 6 yrs; ≥6 to &lt;12 yrs and the Full Analysis Set, respectively.</description>
          <population>Participants from the Full Analysis Set who provided at least data from baseline, Week 5 (or 10-15 EDs, whichever occurred last), Week 12 or Month 6.</population>
          <units>IU/dL : IU/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="31"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline [n= 15; 16; 31]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7675" spread="0.34998"/>
                    <measurement group_id="O2" value="1.9334" spread="0.30000"/>
                    <measurement group_id="O3" value="1.8532" spread="0.33055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5 (or after 10-15 EDs) [n= 27; 30; 57]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9273" spread="0.32400"/>
                    <measurement group_id="O2" value="1.9960" spread="0.39258"/>
                    <measurement group_id="O3" value="1.9635" spread="0.36021"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 [n= 26; 31; 57]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8794" spread="0.24281"/>
                    <measurement group_id="O2" value="1.9869" spread="0.42300"/>
                    <measurement group_id="O3" value="1.9379" spread="0.35368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6 (Termination/Completion) [n= 27; 28; 55]</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8359" spread="0.29188"/>
                    <measurement group_id="O2" value="2.0659" spread="0.45723"/>
                    <measurement group_id="O3" value="1.9530" spread="0.39876"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Pharmacokinetics (PK): Plasma Half-life Ratio of BAX 855 to ADVATE</title>
        <description>This is a descriptive summary of the ratio of plasma half-life in the same subject for BAX 855 compared to ADVATE based on the final covariate model (first observation tabulation).</description>
        <time_frame>(1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4</time_frame>
        <population>Pharmacokinetic (PK) Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>PK Analysis Set</title>
            <description>Participants who had been treated with at least 1 dose of ADVATE (60 ±5 IU/kg) and 1 dose of BAX 855 (60 ±5 IU/kg) in the pharmacokinetic (PK) part of the study (prior to prophylactic treatment) and had at least 1 PK concentration available for population PK and non-compartmental analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics (PK): Plasma Half-life Ratio of BAX 855 to ADVATE</title>
          <description>This is a descriptive summary of the ratio of plasma half-life in the same subject for BAX 855 compared to ADVATE based on the final covariate model (first observation tabulation).</description>
          <population>Pharmacokinetic (PK) Analysis Set</population>
          <units>hours (hr)</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>One stage clotting assay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.30" lower_limit="0.944" upper_limit="2.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chromogenic assay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" lower_limit="0.894" upper_limit="4.810"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Throughout the study period of 1 year (8-10 months per participant)</time_frame>
      <desc>AEs were continuously monitored but specifically discussed and reviewed at these time points: pre- and post-PK infusion, at the baseline visit, during prophylactic treatment at these visits: Week 5 (or 10-15 exposure days (EDs)), Week 12, Week 20 (by phone); at the study completion visit at Month 6 or after at least 50 EDs, whichever occurred last.</desc>
      <group_list>
        <group group_id="E1">
          <title>BAX 855 Safety Analysis Set</title>
          <description>Participants who received at least 1 dose of BAX 855.</description>
        </group>
        <group group_id="E2">
          <title>ADVATE Received Before BAX 855</title>
          <description>Participants who received at least 1 dose of ADVATE prior to receiving BAX 855 in the PK part of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="30" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="13" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </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="5" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </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>Baxalta's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, results may not be published without prior written approval of Sponsor.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Shire</organization>
      <phone>+1 866 842 5335</phone>
      <email>ClinicalTransparency@shire.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/NCT02210091
org study id: 261202
secondary id: 2014-000742-30
nct id: NCT02210091
lead sponsor: 
has dmc: Yes
The study purpose is:

        -  To assess the incidence of FVIII inhibitory antibodies during 6 months of twice weekly
           prophylactic treatment with BAX 855 or 50 exposure days (EDs), whichever occurs last.

        -  To compare pharmacokinetic (PK) parameters to ADVATE.

        -  To assess hemostatic efficacy in prophylaxis and the treatment of bleeding episodes.

        -  To evaluate safety and immunogenicity.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
description: Inhibitory antibodies to FVIII were measured using the Nijmegen modification of the Bethesda assay. Incidence of an FVIII inhibitory antibody was defined as an inhibitor level ≥0.6 Bethesda units [BU].
measure: Annualized Bleeding Rate (ABR)
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
description: The annualized bleeding rate (ABR) during the prophylaxis period was assessed based upon each individual bleeding episode, spontaneous or traumatic, recorded in the participant´s diary and/or recorded in the physician/nurse/study site notes. The annualized bleeding rate was analyzed using a generalized linear model framework assuming a negative binomial distribution with a logarithmic link function and presence or absence of target joints and age cohort as covariates and duration of the observation period in years as offset. Point estimates for the mean and 95% confidence intervals are presented.
measure: Consumption of BAX 855: Number of Prophylactic Infusions Per Month Per Participant
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Consumption of BAX 855: Number of Prophylactic Infusions Per Year (Annualized) Per Participant
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Month Per Participant
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Consumption of BAX 855: Weight-adjusted Dose of Prophylactic Infusions Per Year (Annualized) Per Participant
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Consumption of BAX 855: Number of Infusions Per Bleeding Episode
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Consumption of BAX 855: Weight-adjusted Dose Per Bleeding Episode
time frame: During prophylaxis period of 6 months or ≥ 50 EDs, whichever occurs last
measure: Hemostatic Efficacy Rating for Bleeding Episodes Treated With BAX 855 at Resolution of Bleed
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
description: Rating Scale for Treatment of Bleeding Episodes (BEs) (4-point ordinal scale): Excellent: Full relief of pain and cessation of objective signs of bleeding (eg, swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis did not affect this scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.
measure: Serious Adverse Events (SAEs) Possibly or Probably Related to BAX 855
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
measure: Non-serious Adverse Events Possibly or Probably Related to BAX 855
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
measure: Number of Participants With Clinically Significant Changes in Vital Signs
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
description: Vital signs: body temperature (°C), respiratory rate (breaths/min), pulse rate (beats/min), and systolic and diastolic blood pressure (mmHg). For each vital sign value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant (i.e. and adverse event), or not.
measure: Number of Clinically Significant Changes in Clinical Laboratory Parameters (Hematology, Clinical Chemistry, Lipids)
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
description: The HEMATOLOGY PANEL consisted of complete blood count: hemoglobin, hematocrit, erythrocytes (ie, red blood cell count), leukocytes (ie, white blood cell count) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, and neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration, and platelet count. The CLINICAL CHEMISTRY PANEL consisted of sodium, potassium, chloride, bicarbonate, total protein, albumin, ALT, aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine, and glucose. The LIPID PANEL consisted of cholesterol, very low density lipoprotein, low density lipoprotein, high density lipoprotein, and triglycerides. For each laboratory parameter value that changed from normal at baseline to abnormal at any subsequent study visit, the Investigator determined if the value was clinically significant, or not.
measure: Positive Post-baseline Binding Antibodies to Factor VIII (FVIII), Polyethylene Glycol-Factor VIII (PEG-FVIII), PEG and Chinese Hamster Ovary (CHO) Proteins
time frame: After first exposure to BAX 855 until completion of study - approx. 6 months per participant.
description: Binding antibodies to FVIII and PEG-FVIII, as well as to PEG, were measured using enzyme-linked immunosorbent assay (ELISA). Both immunoglobulin G (IgG) and immunoglobulin M (IgM) binding antibodies for FVIII, BAX 855, and PEG were tested at each study visit. Testing for binding antibodies to CHO was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal anti-human IgG antibodies. This outcome measure includes antibodies that were transient (antibody developed after exposure to BAX 855 but not present at study termination/completion) and pre-existent (antibody originally present before exposure to BAX 855).
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion (AUC0-∞)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From 0 to ∞ Hours Post-infusion Per Dose, (AUC0-∞/Dose)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
measure: Pharmacokinetics (PK): Mean Residence Time (MRT)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Clearance (CL)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Plasma Half-life (T1/2)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Volume of Distribution at Steady State (Vss)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A nonlinear mixed effects model approach (population PK) was implemented to analyze PK data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Incremental Recovery (IR)
time frame: (1) within 30 min pre-infusion; (2) 15-30 min post-infusion; (3) Day 0 either 4 or 7 hours post-infusion; Day 1 am; Day 1 pm; (4) Day 2; Day 3; or Day 4
description: The first PK infusion was ADVATE and the second PK infusion was BAX 855. All participants undergoing PK assessment had a 72-hour washout period before administration of ADVATE and BAX 855. There were 4 blood draws for PK analysis-1 pre-infusion and 3 post infusion. The timing of the infusion (morning [am] or afternoon [pm]) and the timing of Blood Draws 3 and 4 (3 groups for each blood draw) were determined at randomization. The sequence was as follows:- Blood Draw 1. within 30 minutes pre-infusion [Day 0]; PK INFUSION - am or pm [Day 0]; Blood Draw 2. 15-30 minutes post-infusion [Day 0]; Blood Draw 3. 3 groups:- 7 hours post-infusion (if am PK infusion) or 4 hours post-infusion (if pm PK infusion) [Day 0], Day 1 am or Day 1 pm; Blood Draw 4. 3 groups:- Day 2, Day 3 or Day 4. A non-compartmental model approach was implemented to analyze IR data. A one-stage clotting assay was used as the primary assay and a chromogenic assay was used to provide supportive data.
measure: Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - One Stage Clotting Assay
time frame: Baseline, Week 5 (or 10-15 EDs, whichever occurs last), Week 12, and Month 6 (Completion/Termination)
description: Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "One stage clotting assay - BAX 855" For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] < 6 yrs; ≥6 to <12 yrs and the Full Analysis Set, respectively.
measure: Pharmacokinetics (PK): Incremental Recovery (IR) of BAX 855 Over Time - Chromogenic Assay
time frame: Baseline, Week 5 (or 10-15 Exposure Days [EDs], whichever occurs last), Week 12, and Month 6 (Completion/Termination)
description: Pre- and post-infusion levels of Factor VIII (FVIII) following infusion of BAX 855 were used to determine IR. For participants who underwent PK evaluation, baseline IR was determined from the IR measurement used in the PK analysis. Refer to data in Outcome measure 21- "Pharmacokinetics (PK): Incremental Recovery (IR)", for the category "Chromogenic assay - BAX 855" For participants who did not undergo a PK evaluation, baseline IR was determined at the baseline visit prior to the prophylactic treatment phase and is included in this outcome measure. Category title includes number of participants [n] < 6 yrs; ≥6 to <12 yrs and the Full Analysis Set, respectively.
arm group label: <6 years old
arm group type: Experimental
arm group label: ≥6 to <12 years
arm group type: Experimental
intervention type: Biological
intervention name: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
description: Pharmacokinetic (PK) analysis of ADVATE
arm group label: <6 years old
arm group label: ≥6 to <12 years
other name: ADVATE
intervention type: Biological
intervention name: PEGylated Recombinant Factor VIII
description: Pharmacokinetic (PK) analysis of BAX 855
arm group label: <6 years old
arm group label: ≥6 to <12 years
other name: BAX 855
intervention type: Biological
intervention name: PEGylated Recombinant Factor VIII
description: Prophylaxis treatment
arm group label: <6 years old
arm group label: ≥6 to <12 years
other name: BAX 855
criteria: 
gender: All
minimum age: N/A
maximum age: 11 Years
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
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country: Bulgaria
country: Hong Kong
country: Korea, Republic of
country: Malaysia
country: Netherlands
country: Spain
country: Taiwan
country: Turkey
country: Ukraine
country: United Kingdom
country: United States
citation: Mullins ES, Stasyshyn O, Alvarez-Roman MT, Osman D, Liesner R, Engl W, Sharkhawy M, Abbuehl BE. Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia. 2017 Mar;23(2):238-246. doi: 10.1111/hae.13119. Epub 2016 Nov 27.
PMID: 27891721
responsible party type: Sponsor
mesh term: Hemophilia A
mesh term: Factor VIII
mesh term: BAX 855
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/
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