<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/NCT03748823</url>
  </required_header>
  <id_info>
    <org_study_id>ALXN1210-PNH-303</org_study_id>
    <nct_id>NCT03748823</nct_id>
  </id_info>
  <brief_title>Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab</brief_title>
  <official_title>A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label, Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alexion</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab&#xD;
      administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously&#xD;
      administered ravulizumab in adult participants with PNH who are clinically stable on&#xD;
      eculizumab for at least 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will consist of an up to 30 day Screening Period, a 10-week Randomized Treatment&#xD;
      Period, and a 172-week Extension Period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Actual">April 14, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ctrough Serum Concentration of Ravulizumab</measure>
    <time_frame>Predose at Day 71</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ctrough Serum Concentration of Ravulizumab at Day 351</measure>
    <time_frame>Predose at Day 351</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Free Serum Complement Component 5 (C5) Concentrations at Day 71</measure>
    <time_frame>Predose at Day 71</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Free Serum Complement Component 5 (C5) Concentrations at Day 351</measure>
    <time_frame>Predose at Day 351</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71</measure>
    <time_frame>Baseline, Day 71</time_frame>
    <description>Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351</measure>
    <time_frame>Baseline, Day 351</time_frame>
    <description>Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71</measure>
    <time_frame>Baseline, Day 71</time_frame>
    <description>FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351</measure>
    <time_frame>Baseline, Day 351</time_frame>
    <description>FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71</measure>
    <time_frame>Baseline, Day 71</time_frame>
    <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351</measure>
    <time_frame>Baseline, Day 351</time_frame>
    <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71</measure>
    <time_frame>Baseline up to Day 71</time_frame>
    <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351</measure>
    <time_frame>Baseline up to Day 351</time_frame>
    <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71</measure>
    <time_frame>Baseline up to Day 71</time_frame>
    <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351</measure>
    <time_frame>Baseline up to Day 351</time_frame>
    <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71</measure>
    <time_frame>Baseline up to Day 71</time_frame>
    <description>Stabilized hemoglobin (SHg) was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351</measure>
    <time_frame>Baseline up to Day 351</time_frame>
    <description>SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">136</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria</condition>
  <arm_group>
    <arm_group_label>Ravulizumab SC Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.&#xD;
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ravulizumab IV Treatment Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.&#xD;
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Ravulizumab OBDS</intervention_name>
    <description>The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.</description>
    <arm_group_label>Ravulizumab IV Treatment Group</arm_group_label>
    <arm_group_label>Ravulizumab SC Treatment Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Ravulizumab</intervention_name>
    <description>Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.</description>
    <arm_group_label>Ravulizumab IV Treatment Group</arm_group_label>
    <arm_group_label>Ravulizumab SC Treatment Group</arm_group_label>
    <other_name>ALXN1210</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female ≥18 years of age&#xD;
&#xD;
          -  Treated with eculizumab for PNH for at least 3 months prior to Day 1&#xD;
&#xD;
          -  LDH level ≤1.5 × upper limit of normal (ULN) at screening&#xD;
&#xD;
          -  PNH diagnosis confirmed by documented high-sensitivity flow cytometry.&#xD;
&#xD;
          -  Documented meningococcal vaccination not more than 3 years prior to, or at the time&#xD;
             of, initiating study treatment.&#xD;
&#xD;
          -  Body weight ≥40 to &lt;100 kilogram (kg)&#xD;
&#xD;
          -  Female participants of childbearing potential must use highly effective contraception&#xD;
             starting at screening and continuing until at least 8 months after the last dose of&#xD;
             ravulizumab.&#xD;
&#xD;
          -  Willing and able to give written informed consent and comply with study visit&#xD;
             schedule.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  LDH level ≤ 2 × upper limit of normal (ULN) within 3 months prior to Day 1&#xD;
&#xD;
          -  History of bone marrow transplantation.&#xD;
&#xD;
          -  History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease&#xD;
             that, in the opinion of the Investigator or Sponsor, would preclude participation.&#xD;
&#xD;
          -  Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal&#xD;
             bleed, severe congestive heart failure, anticipated need for major surgery within 6&#xD;
             months of randomization, coexisting chronic anemia unrelated to PNH).&#xD;
&#xD;
          -  Females who are pregnant, breastfeeding or who have a positive pregnancy test at&#xD;
             screening or Day 1.&#xD;
&#xD;
          -  Participation in another interventional clinical study or use of any experimental&#xD;
             therapy within 30 days before initiation of study drug on Day 1 in this study or&#xD;
             within 5 half-lives of that investigational product, whichever is greater.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Liverpool</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Parkville</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Hasselt</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Botucatu</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Ribeirão Preto</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Rio De Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Salvador</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Pessac</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Pierre-Bénite</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Ekaterinburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Donostia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Las Palmas De Gran Canaria</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Majadahonda</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Uppsala</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Adana</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>İzmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Finland</country>
    <country>France</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <results_first_submitted>August 9, 2022</results_first_submitted>
  <results_first_submitted_qc>October 10, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 20, 2022</results_first_posted>
  <disposition_first_submitted>January 11, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>October 10, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 20, 2022</disposition_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PNH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemoglobinuria</mesh_term>
    <mesh_term>Hemoglobinuria, Paroxysmal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ravulizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 8, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03748823/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT03748823/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants were stratified by weight group (≥40 to &lt;60 kilogram [kg] and ≥60 to &lt;100 kg) and then randomized in a 2:1 ratio to 2 treatment groups. This is an ongoing study and the data presented are the study results from the 10-week Randomized Treatment Period and data from the Extension Period through the data cutoff date at 02 February 2021.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ravulizumab IV/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 milligrams [mg]) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC once every week (qw).</description>
        </group>
        <group group_id="P2">
          <title>Ravulizumab SC/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Randomized Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated and Not Included in Analysis</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="84"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="84"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="90"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Extension Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="89">1 participant withdrew consent prior to entering the Extension Period</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="89"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated But Not Included in the Analysis</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="87"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing in the Extension Period</title>
              <participants_list>
                <participants group_id="P1" count="41"/>
                <participants group_id="P2" count="84"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>Ravulizumab IV/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
        </group>
        <group group_id="B2">
          <title>Ravulizumab SC/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
            <count group_id="B2" value="84"/>
            <count group_id="B3" value="129"/>
          </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="46.4" spread="13.22"/>
                    <measurement group_id="B2" value="45.3" spread="14.47"/>
                    <measurement group_id="B3" value="45.7" spread="14.00"/>
                  </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="25"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="82"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ctrough Serum Concentration of Ravulizumab</title>
        <time_frame>Predose at Day 71</time_frame>
        <population>Pharmacokinetic (PK) analysis set included all participants who had evaluable PK data.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Ctrough Serum Concentration of Ravulizumab</title>
          <population>Pharmacokinetic (PK) analysis set included all participants who had evaluable PK data.</population>
          <units>microgram/milliliter (µg/mL)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="457.58" spread="108.491"/>
                    <measurement group_id="O2" value="578.70" spread="140.819"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>Noninferiority was determined based on the 90% Confidence interval calculated from the combination z-score that accounts for the interim analysis.</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Analysis of variance (ANOVA) was performed on log-transformed Ctrough and included treatment and stratified weight group as fixed effects.</p_value_desc>
            <method>ANOVA</method>
            <param_type>Ratio of Geometric Least Squares Mean</param_type>
            <param_value>1.257</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.160</ci_lower_limit>
            <ci_upper_limit>1.361</ci_upper_limit>
            <estimate_desc>Geometric least squares mean are the least squares mean from the mixed model after back transformation to the original scale. The 90% confidence interval is presented after back transformation to the original scale.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ctrough Serum Concentration of Ravulizumab at Day 351</title>
        <time_frame>Predose at Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Ctrough Serum Concentration of Ravulizumab at Day 351</title>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="712.79" spread="203.180"/>
                    <measurement group_id="O2" value="737.65" spread="208.894"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Free Serum Complement Component 5 (C5) Concentrations at Day 71</title>
        <time_frame>Predose at Day 71</time_frame>
        <population>Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of ravulizumab and who had evaluable PD data. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Free Serum Complement Component 5 (C5) Concentrations at Day 71</title>
          <population>Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of ravulizumab and who had evaluable PD data. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="83"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.072193" spread="0.0245225"/>
                    <measurement group_id="O2" value="0.059458" spread="0.0182180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Free Serum Complement Component 5 (C5) Concentrations at Day 351</title>
        <time_frame>Predose at Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Free Serum Complement Component 5 (C5) Concentrations at Day 351</title>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.071627" spread="0.0227980"/>
                    <measurement group_id="O2" value="0.069711" spread="0.0208784"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71</title>
        <description>Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
        <time_frame>Baseline, Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71</title>
          <description>Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="82"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.73" spread="29.716"/>
                    <measurement group_id="O2" value="2.57" spread="33.883"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351</title>
        <description>Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
        <time_frame>Baseline, Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351</title>
          <description>Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="17.225"/>
                    <measurement group_id="O2" value="1.74" spread="21.905"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71</title>
        <description>FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.</description>
        <time_frame>Baseline, Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71</title>
          <description>FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.83" spread="7.378"/>
                    <measurement group_id="O2" value="1.21" spread="7.882"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351</title>
        <description>FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.</description>
        <time_frame>Baseline, Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351</title>
          <description>FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.57" spread="7.178"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71</title>
        <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
        <time_frame>Baseline, Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71</title>
          <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.00" spread="34.581"/>
                    <measurement group_id="O2" value="-70.54" spread="70.522"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351</title>
        <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
        <time_frame>Baseline, Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351</title>
          <description>The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. This outcome measure was planned to be reported for ravulizumab SC/SC treatment group only.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-69.29" spread="80.068"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71</title>
        <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.</description>
        <time_frame>Baseline up to Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71</title>
          <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="0.06" upper_limit="11.77"/>
                    <measurement group_id="O2" value="1.2" lower_limit="0.03" upper_limit="6.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351</title>
        <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
        <time_frame>Baseline up to Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351</title>
          <description>Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt;10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="0.56" upper_limit="15.47"/>
                    <measurement group_id="O2" value="3.6" lower_limit="0.74" upper_limit="10.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71</title>
        <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.</description>
        <time_frame>Baseline up to Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71</title>
          <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.7" lower_limit="73.21" upper_limit="94.95"/>
                    <measurement group_id="O2" value="94.0" lower_limit="86.65" upper_limit="98.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351</title>
        <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
        <time_frame>Baseline up to Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351</title>
          <description>Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79.5" lower_limit="64.70" upper_limit="90.20"/>
                    <measurement group_id="O2" value="85.7" lower_limit="76.38" upper_limit="92.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71</title>
        <description>Stabilized hemoglobin (SHg) was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.</description>
        <time_frame>Baseline up to Day 71</time_frame>
        <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71</title>
          <description>Stabilized hemoglobin (SHg) was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.</description>
          <population>Full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab, and were not excluded from analysis. Here, Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81.8" lower_limit="67.29" upper_limit="91.81"/>
                    <measurement group_id="O2" value="93.6" lower_limit="85.67" upper_limit="97.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351</title>
        <description>SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.</description>
        <time_frame>Baseline up to Day 351</time_frame>
        <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Ravulizumab IV/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
          <group group_id="O2">
            <title>Ravulizumab SC/SC Treatment Group</title>
            <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351</title>
          <description>SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.</description>
          <population>SC treated full analysis set included all participants who had signed informed consent, were randomized, received at least 1 dose of ravulizumab SC, and were not excluded from analysis. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.7" lower_limit="57.21" upper_limit="85.04"/>
                    <measurement group_id="O2" value="83.5" lower_limit="73.51" upper_limit="90.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Day 365 (data cutoff date)</time_frame>
      <desc>Safety analysis set included all participants who received at least 1 dose of ravulizumab and were not excluded from analysis. Adverse events (AEs) are reported for the entire study period by the participant's randomized treatment group during the controlled portion of the study. AEs are reported through the 52 week data cutoff date.</desc>
      <group_list>
        <group group_id="E1">
          <title>Ravulizumab IV/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab IV on Day 1, followed by a maintenance weight-based dose (3000 to 3300 mg) of ravulizumab IV on Day 15. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
        </group>
        <group group_id="E2">
          <title>Ravulizumab SC/SC Treatment Group</title>
          <description>During the Randomized Treatment Period, participants received a weight-based single loading dose (2400 to 2700 mg) of ravulizumab SC on Day 1, followed by maintenance weight-based doses (490 mg) of ravulizumab SC qw from Days 15 to 64. During the Extension Period (Day 71 up to Day 1275), participants received 490 mg of ravulizumab SC qw.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Haemolysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Aplastic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Haemolytic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lens dislocation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Application site induration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Hepatitis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Salmonellosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Suspected COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Tubo-ovarian abscess</sub_title>
                <description>This adverse event is gender specific.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Transfusion reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Colon adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Lung adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cervicobrachial syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Adnexal torsion</sub_title>
                <description>This adverse event is gender specific.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</default_vocab>
        <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="43" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="74" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Haemolysis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device delivery system issue</sub_title>
                <description>Adverse Events relating to drug delivery were coded to the MedDRA SOC of &quot;Product Issues&quot;, including missing dose (ie, no dose) and partial dose (ie, less than full volume of dose administered) medication errors occurring with use of device.</description>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Incorrect dose administered by device</sub_title>
                <description>Adverse Events relating to drug delivery were coded to the MedDRA SOC of &quot;Product Issues&quot;, including missing dose (ie, no dose) and partial dose (ie, less than full volume of dose administered) medication errors occurring with use of device.</description>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Drug dose omission by device</sub_title>
                <description>Adverse Events relating to drug delivery were coded to the MedDRA SOC of &quot;Product Issues&quot;, including missing dose (ie, no dose) and partial dose (ie, less than full volume of dose administered) medication errors occurring with use of device.</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="84"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="84"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="45"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="84"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>To ensure the quality of the study results, all 7 participants from a noncompliant investigative site were excluded from all prespecified analysis sets due to important source documentation deviations.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Alexion Pharmaceuticals Inc.</name_or_title>
      <organization>Alexion Pharmaceuticals Inc.</organization>
      <phone>855-752-2356</phone>
      <email>clinicaltrials@alexion.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/NCT03748823
org study id: ALXN1210-PNH-303
nct id: NCT03748823
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab
      administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously
      administered ravulizumab in adult participants with PNH who are clinically stable on
      eculizumab for at least 6 months.
The study will consist of an up to 30 day Screening Period, a 10-week Randomized Treatment
      Period, and a 172-week Extension Period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ctrough Serum Concentration of Ravulizumab
time frame: Predose at Day 71
measure: Ctrough Serum Concentration of Ravulizumab at Day 351
time frame: Predose at Day 351
measure: Free Serum Complement Component 5 (C5) Concentrations at Day 71
time frame: Predose at Day 71
measure: Free Serum Complement Component 5 (C5) Concentrations at Day 351
time frame: Predose at Day 351
measure: Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71
time frame: Baseline, Day 71
description: Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.
measure: Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351
time frame: Baseline, Day 351
description: Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71
time frame: Baseline, Day 71
description: FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351
time frame: Baseline, Day 351
description: FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.
measure: Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71
time frame: Baseline, Day 71
description: The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.
measure: Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351
time frame: Baseline, Day 351
description: The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.
measure: Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71
time frame: Baseline up to Day 71
description: Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.
measure: Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351
time frame: Baseline up to Day 351
description: Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.
measure: Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71
time frame: Baseline up to Day 71
description: Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.
measure: Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351
time frame: Baseline up to Day 351
description: Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.
measure: Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71
time frame: Baseline up to Day 71
description: Stabilized hemoglobin (SHg) was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.
measure: Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351
time frame: Baseline up to Day 351
description: SHg was defined as the avoidance of a ≥2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.
arm group label: Ravulizumab SC Treatment Group
arm group type: Experimental
description: In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
arm group label: Ravulizumab IV Treatment Group
arm group type: Active Comparator
description: In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15.
In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.
intervention type: Combination Product
intervention name: Ravulizumab OBDS
description: The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.
arm group label: Ravulizumab IV Treatment Group
arm group label: Ravulizumab SC Treatment Group
intervention type: Biological
intervention name: Ravulizumab
description: Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.
arm group label: Ravulizumab IV Treatment Group
arm group label: Ravulizumab SC Treatment Group
other name: ALXN1210
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Australia
country: Austria
country: Belgium
country: Brazil
country: Canada
country: Finland
country: France
country: Italy
country: Netherlands
country: Russian Federation
country: Spain
country: Sweden
country: Turkey
country: United States
responsible party type: Sponsor
mesh term: Hemoglobinuria
mesh term: Hemoglobinuria, Paroxysmal
mesh term: Ravulizumab
sharing ipd: No
provided document: 
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participant flow: 
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outcome list: 
reported events: 
certain agreements: 
limitations and caveats: To ensure the quality of the study results, all 7 participants from a noncompliant investigative site were excluded from all prespecified analysis sets due to important source documentation deviations.
point of contact: 