<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/NCT04469465</url>
  </required_header>
  <id_info>
    <org_study_id>ALXN2040-PNH-301</org_study_id>
    <secondary_id>2019-003829-18</secondary_id>
    <nct_id>NCT04469465</nct_id>
  </id_info>
  <brief_title>Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)</brief_title>
  <official_title>A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alexion</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy&#xD;
      to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with&#xD;
      PNH who have clinically evident EVH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multiple-region, randomized, double-blind, placebo controlled, multiple-dose, study&#xD;
      in participants with PNH who have clinically evident EVH on a C5 inhibitor (eculizumab or&#xD;
      ravulizumab).&#xD;
&#xD;
      Participants will be randomized to receive danicopan or placebo, in a 2:1 ratio for 12 weeks&#xD;
      (Treatment Period 1) in addition to their C5 inhibitor (eculizumab or ravulizumab) therapy.&#xD;
      At Week 12, participants randomized to receive placebo will be switched to danicopan in&#xD;
      addition to their C5 inhibitor for an additional 12 weeks (Treatment Period 2) and&#xD;
      participants randomized to danicopan will continue on danicopan for an additional 12 weeks,&#xD;
      while remaining on their ongoing C5 inhibitor therapy.&#xD;
&#xD;
      At the end of the 2 treatment periods (Week 24), participants may enter a Long-Term Extension&#xD;
      (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy. The&#xD;
      Long-Term Extension period will consist of a first year of LTE(Year1) and a second year of&#xD;
      optional LTE(Year2).All patients will complete 72 weeks of LTE(Year 1) assessments. After&#xD;
      Week 72 (at the end of the first year of LTE), patients have the choice to complete&#xD;
      participation in this study or continue to the optional second year (Year2) of LTE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 16, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">June 28, 2022</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Hgb at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hgb Increase of ≥2 g/dL (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Transfusion Avoidance Through Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue better health-related quality of life. LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Absolute Reticulocyte Count at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment</measure>
    <time_frame>24 weeks prior to initiation of treatment to post 24 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment</measure>
    <time_frame>24 weeks prior to initiation of treatment to post 24 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Transfusion Avoidance Through Week 24</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</measure>
    <time_frame>12 weeks prior to initiation of treatment to post 12 weeks of treatment</time_frame>
    <description>LS mean and SE were produced using analysis of covariance (ANCOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</measure>
    <time_frame>12 weeks prior to initiation of treatment to post 12 weeks of treatment</time_frame>
    <description>LS mean and SE were produced using ANCOVA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline FACIT Fatigue Scores at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan</measure>
    <time_frame>Week 12 to Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total and Direct Bilirubin at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in C3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Lactate Dehydrogenase at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hgb Normalization at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 grams (g)/liter (L), for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hgb Normalization at Week 24</measure>
    <time_frame>Week 24</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria</condition>
  <arm_group>
    <arm_group_label>Danicopan + C5 Inhibitor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + C5 Inhibitor</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Danicopan</intervention_name>
    <description>Oral tablet</description>
    <arm_group_label>Danicopan + C5 Inhibitor</arm_group_label>
    <other_name>ALXN2040</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral tablet</description>
    <arm_group_label>Placebo + C5 Inhibitor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>C5 Inhibitor</intervention_name>
    <description>Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.</description>
    <arm_group_label>Danicopan + C5 Inhibitor</arm_group_label>
    <arm_group_label>Placebo + C5 Inhibitor</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PNH&#xD;
&#xD;
          -  Clinically Evident EVH defined by:&#xD;
&#xD;
               -  Anemia (Hgb ≤9.5 gram/deciliter) with absolute reticulocyte count ≥120 x&#xD;
                  10^9/liter&#xD;
&#xD;
          -  Receiving an approved C5 inhibitor for at least 6 months prior to Day 1&#xD;
&#xD;
          -  Platelet count ≥30,000/microliters (µL)&#xD;
&#xD;
          -  Absolute neutrophil counts ≥500/μL&#xD;
&#xD;
          -  Documentation of/or willingness to receive vaccinations for N. meningiditis and&#xD;
             prophylactic antibiotics as required&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of a major organ transplant or hematopoietic stem cell transplantation (HSCT)&#xD;
&#xD;
          -  Participants with known aplastic anemia or other bone marrow failure that requires&#xD;
             HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants&#xD;
&#xD;
          -  Known or suspected complement deficiency&#xD;
&#xD;
          -  Laboratory abnormalities at screening, including:&#xD;
&#xD;
               -  Alanine aminotransferase &gt;2 x ULN (&gt;3 x ULN in case of patients with documented&#xD;
                  liver iron overload defined by serum ferratin values&#xD;
&#xD;
                    -  500 ng/ML)&#xD;
&#xD;
               -  Direct bilirubin &gt;2 x ULN (unless due to EVH or documented Gilbert's Syndrome)&#xD;
&#xD;
          -  Current evidence of biliary cholestasis&#xD;
&#xD;
          -  Estimated glomerular filtration rate of &lt;30 milliliters/minute/1.73 meter squared&#xD;
             and/or are on dialysis&#xD;
&#xD;
          -  Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection&#xD;
             at screening&#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>Weston</city>
        <state>Florida</state>
        <zip>33331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Salvador</city>
        <state>Bahia</state>
        <zip>40170-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Fortaleza</city>
        <state>Ceara</state>
        <zip>60430-370</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Goiania</city>
        <state>Goias</state>
        <zip>74605-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <zip>80810-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Belem</city>
        <state>Para</state>
        <zip>66053-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90110-270</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20211-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2G3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>MSG 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Brno</city>
        <zip>62500</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Nice</city>
        <state>Alpes Maritimes</state>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Marseille Cedex 9</city>
        <state>Bouches-du-Rhone</state>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Lille cedex</city>
        <state>Nord</state>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Paris cedex 10</city>
        <state>Paris</state>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Pierre-Bénite</city>
        <state>Rhone</state>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Athens</city>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Haifa</city>
        <zip>31048</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Jerusalem</city>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Reggio Calabria</city>
        <state>Calabria</state>
        <zip>89214</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Avellino</city>
        <state>Campagnia</state>
        <zip>83100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Bassano Del Grappa</city>
        <state>Vicenza</state>
        <zip>36061</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Nagakute-shi</city>
        <state>Aichi</state>
        <zip>480-1195</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Toyoake</city>
        <state>Aichi</state>
        <zip>470-1192</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kashiwa-shi</city>
        <state>Chiba</state>
        <zip>277-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Fukuoka-shi</city>
        <state>Fukuoka</state>
        <zip>812-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Fukushima-shi</city>
        <state>Fukushima-ken</state>
        <zip>960-1295</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Ogaki-shi</city>
        <state>Gifu</state>
        <zip>503-8502</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Tsukuba-shi</city>
        <state>Ibaraki</state>
        <zip>305-8576</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kyoto-shi</city>
        <state>Kyoto-Fu</state>
        <zip>605-0981</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>530-8480</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Osakasayama-shi</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Suita-shi</city>
        <state>Osaka</state>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Bunkyo-ku</city>
        <state>Tokyo</state>
        <zip>113-8603</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Shibuya-ku</city>
        <state>Tokyo</state>
        <zip>150-8935</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Shinjuku-Ku</city>
        <state>Tokyo</state>
        <zip>160-0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Tanabe-shi</city>
        <state>Wakayama</state>
        <zip>646-8588</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Suwon-si</city>
        <state>Gyeonggi-do</state>
        <zip>16247</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Daejeon</city>
        <zip>35015</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Seoul</city>
        <zip>06591</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kota Kinabalu</city>
        <state>Sabah</state>
        <zip>88586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>93588</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Miri</city>
        <state>Sarawak</state>
        <zip>98000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Las Palmas</city>
        <state>Las Palmas De Gran Canaria</state>
        <zip>35019</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Málaga</city>
        <state>Malaga</state>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Pathum Wan</city>
        <state>Bangkok</state>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>SE5 9NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Airdrie</city>
        <state>North Lanarkshire</state>
        <zip>ML6 0JS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Site</name>
      <address>
        <city>Leeds</city>
        <state>West Yorkshire</state>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://doi.org/10.1182/blood-2019-124837</url>
    <description>Mechanistic Evaluation of Efficacy Using Biomarkers of the Oral, Small Molecule Factor D Inhibitor, Danicopan (ACH-4471), in Untreated Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)</description>
  </link>
  <link>
    <url>https://doi.org/10.1182/blood-2019-124748</url>
    <description>A Phase 2 Open-Label Study of Danicopan (ACH-0144471) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy</description>
  </link>
  <link>
    <url>https://library.ehaweb.org/eha/2019/24th/267447/peter.browett.a.phase.2.open</url>
    <description>Danicopan (ACH-4471) in Untreated Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Phase 2, Open-label, Proof of Concept Study of the Oral, Small Molecule Factor D Inhibitor</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <results_first_submitted>June 28, 2023</results_first_submitted>
  <results_first_submitted_qc>July 21, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 24, 2023</results_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Paroxysmal Nocturnal Hemoglobinuria (PNH)</keyword>
  <keyword>Extravascular Hemolysis (EVH)</keyword>
  <keyword>Factor D inhibitor</keyword>
  <keyword>Complement</keyword>
  <keyword>Danicopan</keyword>
  <keyword>C5 inhibitor</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>
    <mesh_term>Hemolysis</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 8, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04469465/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>August 10, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT04469465/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study consists of 2 treatment periods and a Long-term Extension (LTE) period. This study is ongoing, and the results of treatment period 1 (up to Week 12) have been reported here. The final results will be reported after the completion of study.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Danicopan</title>
          <description>Participants received danicopan 3 times daily (TID) for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received at Least 1 Dose of Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Interim Efficacy Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing treatment</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety set included all participants that received at least 1 dose of study drug (danicopan or placebo).</population>
      <group_list>
        <group group_id="B1">
          <title>Danicopan</title>
          <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</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="57"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="86"/>
          </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="52.8" spread="17.00"/>
                    <measurement group_id="B2" value="52.9" spread="14.34"/>
                    <measurement group_id="B3" value="52.8" spread="16.07"/>
                  </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="34"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="32"/>
                  </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="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </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="22"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="32"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hemoglobin (Hgb)</title>
          <units>grams (g)/liter (L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="76.7" spread="9.47"/>
                    <measurement group_id="B2" value="78.9" spread="10.11"/>
                    <measurement group_id="B3" value="77.5" spread="9.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Hgb at Week 12</title>
        <description>Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hgb at Week 12</title>
          <description>Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
          <units>g/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.40" spread="2.107"/>
                    <measurement group_id="O2" value="4.96" spread="3.128"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.0007</p_value>
            <method>Re-randomization test</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>24.44</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.751</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>16.90</ci_lower_limit>
            <ci_upper_limit>31.99</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hgb Increase of ≥2 g/dL (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12</title>
        <description>The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.</description>
        <time_frame>Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Hgb Increase of ≥2 g/dL (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12</title>
          <description>The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy 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="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.5" lower_limit="43.28" upper_limit="74.37"/>
                    <measurement group_id="O2" value="0" lower_limit="0.00" upper_limit="16.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Transfusion Avoidance Through Week 12</title>
        <description>Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.</description>
        <time_frame>Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Transfusion Avoidance Through Week 12</title>
          <description>Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy 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="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.3" lower_limit="68.64" upper_limit="93.03"/>
                    <measurement group_id="O2" value="38.1" lower_limit="18.11" upper_limit="61.56"/>
                  </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 Score at Week 12</title>
        <description>The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue better health-related quality of life. LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12</title>
          <description>The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue better health-related quality of life. LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.97" spread="1.128"/>
                    <measurement group_id="O2" value="1.85" spread="1.581"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Absolute Reticulocyte Count at Week 12</title>
        <description>LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Absolute Reticulocyte Count at Week 12</title>
          <description>LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
          <units>10^12 cells/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0838" spread="0.00893"/>
                    <measurement group_id="O2" value="0.0035" spread="0.01268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment</title>
        <time_frame>24 weeks prior to initiation of treatment to post 24 weeks of treatment</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment</title>
        <time_frame>24 weeks prior to initiation of treatment to post 24 weeks of treatment</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Transfusion Avoidance Through Week 24</title>
        <time_frame>Week 24</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</title>
        <description>LS mean and SE were produced using analysis of covariance (ANCOVA).</description>
        <time_frame>12 weeks prior to initiation of treatment to post 12 weeks of treatment</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</title>
          <description>LS mean and SE were produced using analysis of covariance (ANCOVA).</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
          <units>RBC units</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.48" spread="0.271"/>
                    <measurement group_id="O2" value="-0.18" spread="0.383"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</title>
        <description>LS mean and SE were produced using ANCOVA.</description>
        <time_frame>12 weeks prior to initiation of treatment to post 12 weeks of treatment</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment</title>
          <description>LS mean and SE were produced using ANCOVA.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
          <units>transfusion instances</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.92" spread="0.174"/>
                    <measurement group_id="O2" value="-0.21" spread="0.246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline FACIT Fatigue Scores at Week 24</title>
        <time_frame>Baseline, Week 24</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan</title>
        <time_frame>Week 12 to Week 24</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24</title>
        <time_frame>Week 24</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total and Direct Bilirubin at Week 12</title>
        <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total and Direct Bilirubin at Week 12</title>
          <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
          <units>micromoles (μmol)/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Bilirubin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.77" spread="1.692"/>
                    <measurement group_id="O2" value="-2.15" spread="2.377"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Direct Bilirubin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.88" spread="0.357"/>
                    <measurement group_id="O2" value="0.30" spread="0.503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12</title>
        <description>The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12</title>
          <description>The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
          <units>percentage of the total cell population</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.60" spread="4.180"/>
                    <measurement group_id="O2" value="-3.04" spread="5.864"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in C3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12</title>
        <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in C3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12</title>
          <description>Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
          <units>percentage of the total cell population</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.06" spread="2.824"/>
                    <measurement group_id="O2" value="0.89" spread="4.394"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Lactate Dehydrogenase at Week 12</title>
        <description>Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Lactate Dehydrogenase at Week 12</title>
          <description>Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.</population>
          <units>units (U)/L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.49" spread="8.287"/>
                    <measurement group_id="O2" value="-2.92" spread="11.914"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hgb Normalization at Week 12</title>
        <description>Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 grams (g)/liter (L), for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.</description>
        <time_frame>Week 12</time_frame>
        <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Danicopan</title>
            <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Hgb Normalization at Week 12</title>
          <description>Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 grams (g)/liter (L), for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.</description>
          <population>Interim Efficacy Analysis Set: Per the prespecified plan for interim analysis, the first 75% of randomized participants formed the Interim Analysis Set for efficacy 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="42"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="15.72" upper_limit="44.58"/>
                    <measurement group_id="O2" value="0" lower_limit="0.00" upper_limit="16.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hgb Normalization at Week 24</title>
        <time_frame>Week 24</time_frame>
        <posting_date>12/2024</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Week 12</time_frame>
      <desc>The safety set included all participants that received at least 1 dose of study drug (danicopan or placebo).&#xD;
The AE data of treatment period 1 (up to Week 12) has been reported here. The final AE data will be reported after the completion of study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Danicopan</title>
          <description>Participants received danicopan TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received placebo TID for 12 weeks, in addition to their background eculizumab or ravulizumab therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </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="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </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="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 25.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemolysis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Splenomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Noninfective gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Salivary gland pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Discoloured vomit</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </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="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vessel puncture site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Localised infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Genital herpes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Tooth abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Febrile nonhaemolytic transfusion reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Post procedural contusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Post procedural diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>SARS-CoV-2 test positive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypercholesterolaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Muscle fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Osteopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hallucination</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chromaturia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Haemoglobinuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sinus pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyshidrotic eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pallor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="29"/>
              </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>
    <point_of_contact>
      <name_or_title>Alexion Pharmaceuticals Inc.</name_or_title>
      <organization>Alexion Pharmaceuticals Inc.</organization>
      <phone>+1 855-752-2356</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/NCT04469465
org study id: ALXN2040-PNH-301
secondary id: 2019-003829-18
nct id: NCT04469465
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy
      to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with
      PNH who have clinically evident EVH.
This is a multiple-region, randomized, double-blind, placebo controlled, multiple-dose, study
      in participants with PNH who have clinically evident EVH on a C5 inhibitor (eculizumab or
      ravulizumab).

      Participants will be randomized to receive danicopan or placebo, in a 2:1 ratio for 12 weeks
      (Treatment Period 1) in addition to their C5 inhibitor (eculizumab or ravulizumab) therapy.
      At Week 12, participants randomized to receive placebo will be switched to danicopan in
      addition to their C5 inhibitor for an additional 12 weeks (Treatment Period 2) and
      participants randomized to danicopan will continue on danicopan for an additional 12 weeks,
      while remaining on their ongoing C5 inhibitor therapy.

      At the end of the 2 treatment periods (Week 24), participants may enter a Long-Term Extension
      (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy. The
      Long-Term Extension period will consist of a first year of LTE(Year1) and a second year of
      optional LTE(Year2).All patients will complete 72 weeks of LTE(Year 1) assessments. After
      Week 72 (at the end of the first year of LTE), patients have the choice to complete
      participation in this study or continue to the optional second year (Year2) of LTE.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Hgb at Week 12
time frame: Baseline, Week 12
description: Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.
measure: Percentage of Participants With Hgb Increase of ≥2 g/dL (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12
time frame: Week 12
description: The criterion was defined as ≥20 g/L increase in Hgb from Baseline to Week 12 and remaining transfusion free during the 12-Week TP1. Participants who withdrew from the study early during the 12-Week TP1 or had missing Hgb value at Week 12 were considered as not achieving the criterion.
measure: Percentage of Participants With Transfusion Avoidance Through Week 12
time frame: Week 12
description: Participants achieved transfusion avoidance if they remained transfusion free and did not require a transfusion as per protocol-specified guidelines from Week 1 through Week 12. Participants who discontinued study treatment early before Week 12 were considered as not achieving transfusion avoidance.
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12
time frame: Baseline, Week 12
description: The FACIT-Fatigue was 13-item questionnaire scored on a 5-point Likert scale (0 = not at all, 4 = very much) that assesses self-reported fatigue and its impact on daily activities and function. Total scores range from 0 to 52 with higher score indicating less fatigue better health-related quality of life. LS mean and SE were produced using MMRM.
measure: Change From Baseline in Absolute Reticulocyte Count at Week 12
time frame: Baseline, Week 12
description: LS mean and SE were produced using MMRM.
measure: Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
time frame: 24 weeks prior to initiation of treatment to post 24 weeks of treatment
measure: Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment
time frame: 24 weeks prior to initiation of treatment to post 24 weeks of treatment
measure: Percentage of Participants With Transfusion Avoidance Through Week 24
time frame: Week 24
measure: Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment
time frame: 12 weeks prior to initiation of treatment to post 12 weeks of treatment
description: LS mean and SE were produced using analysis of covariance (ANCOVA).
measure: Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment
time frame: 12 weeks prior to initiation of treatment to post 12 weeks of treatment
description: LS mean and SE were produced using ANCOVA.
measure: Change From Baseline FACIT Fatigue Scores at Week 24
time frame: Baseline, Week 24
measure: Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan
time frame: Week 12 to Week 24
measure: Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24
time frame: Week 24
measure: Change From Baseline in Total and Direct Bilirubin at Week 12
time frame: Baseline, Week 12
description: Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.
measure: Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12
time frame: Baseline, Week 12
description: The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.
measure: Change From Baseline in C3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12
time frame: Baseline, Week 12
description: Baseline was defined as the last nonmissing value prior to first dose of study intervention. LS mean and SE were produced using MMRM.
measure: Change From Baseline in Lactate Dehydrogenase at Week 12
time frame: Baseline, Week 12
description: Baseline was defined as the average of all available assessments prior to the first dose of study intervention. LS mean and SE were produced using MMRM.
measure: Percentage of Participants With Hgb Normalization at Week 12
time frame: Week 12
description: Hgb normalization was defined as Hgb value above lower limit of normal (LLN) reference range. For male, the LLN was 125 grams (g)/liter (L), for female, the LLN was 110 g/L. Participants with transfusions within 4 weeks prior to Week 12 were considered as not meeting Hgb normalization regardless of actual value observed at Week 12.
measure: Percentage of Participants With Hgb Normalization at Week 24
time frame: Week 24
arm group label: Danicopan + C5 Inhibitor
arm group type: Experimental
description: Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2).
arm group label: Placebo + C5 Inhibitor
arm group type: Placebo Comparator
description: Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2).
intervention type: Drug
intervention name: Danicopan
description: Oral tablet
arm group label: Danicopan + C5 Inhibitor
other name: ALXN2040
intervention type: Drug
intervention name: Placebo
description: Oral tablet
arm group label: Placebo + C5 Inhibitor
intervention type: Drug
intervention name: C5 Inhibitor
description: Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule.
arm group label: Danicopan + C5 Inhibitor
arm group label: Placebo + C5 Inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Brazil
country: Canada
country: Czechia
country: France
country: Germany
country: Greece
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Malaysia
country: Netherlands
country: Poland
country: Spain
country: Taiwan
country: Thailand
country: United Kingdom
country: United States
url: https://doi.org/10.1182/blood-2019-124837
description: Mechanistic Evaluation of Efficacy Using Biomarkers of the Oral, Small Molecule Factor D Inhibitor, Danicopan (ACH-4471), in Untreated Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
url: https://doi.org/10.1182/blood-2019-124748
description: A Phase 2 Open-Label Study of Danicopan (ACH-0144471) in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
url: https://library.ehaweb.org/eha/2019/24th/267447/peter.browett.a.phase.2.open
description: Danicopan (ACH-4471) in Untreated Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Phase 2, Open-label, Proof of Concept Study of the Oral, Small Molecule Factor D Inhibitor
responsible party type: Sponsor
mesh term: Hemoglobinuria
mesh term: Hemoglobinuria, Paroxysmal
mesh term: Hemolysis
provided document: 
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certain agreements: 
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