<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/NCT04434092</url>
  </required_header>
  <id_info>
    <org_study_id>BO42162</org_study_id>
    <secondary_id>2019-004931-21</secondary_id>
    <nct_id>NCT04434092</nct_id>
  </id_info>
  <brief_title>A Phase III Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors.</brief_title>
  <acronym>COMMODORE 2</acronym>
  <official_title>A Phase III, Randomized, Open-Label, Active-Controlled, Multicenter Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chugai Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <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>
      A study designed to evaluate the non-inferiority of crovalimab compared with eculizumab in&#xD;
      participants with PNH who have not been previously treated with complement inhibitor therapy.&#xD;
      This study will enroll approximately 200 participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2028</completion_date>
  <primary_completion_date type="Actual">November 16, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants who achieve Transfusion Avoidance (TA)</measure>
    <time_frame>Baseline through Week 25</time_frame>
    <description>TA is defined as patients who are packed Red Blood Cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with hemolysis control</measure>
    <time_frame>Week 5 through Week 25</time_frame>
    <description>Measured by LDH =&lt; 1.5 x ULN (as measured at the central laboratory).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Breakthrough Hemolysis (BTH)</measure>
    <time_frame>Baseline through Week 25</time_frame>
    <description>BTH is defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin &lt; 10 g/dL], a major adverse vascular event [MAVE; including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH &gt;= 2 x ULN after prior reduction of LDH to =&lt;1.5 x ULN on treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Stabilization of Hemoglobin</measure>
    <time_frame>Baseline through Week 25</time_frame>
    <description>Stabilized hemoglobin is defined as avoidance of a &gt;= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Fatigue</measure>
    <time_frame>Baseline up to Week 25</time_frame>
    <description>Assessed by the FACIT-Fatigue Questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events (AEs)</measure>
    <time_frame>Up to 7 years</time_frame>
    <description>Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)</measure>
    <time_frame>Up to 7 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation</measure>
    <time_frame>Up to 7 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with clinical manifestations of Drug-Target-Drug Complex (DTDC) formation amongst those participants who switched to crovalimab treatment from eculizumab treatment</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentrations of crovalimab and eculizumab over time</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Anti-Crovalimab Antibodies</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PD biomarkers including complement activity (CH50) over time</measure>
    <time_frame>Up to 6.5 years</time_frame>
    <description>Assessed by a Liposome Immunoassay (LIA) and total C5 concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change over time in free C5 concentration in crovalimab-treated participants</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Value in Reticulocyte Count (count/mL)</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)</measure>
    <time_frame>Up to 6.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Reticulocyte Count (count/mL)</measure>
    <time_frame>Baseline up to Week 25</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Free Hemoglobin and Haptoglobin (mg/dL)</measure>
    <time_frame>Baseline up to Week 25</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">214</enrollment>
  <condition>Paroxysmal Nocturnal Hemoglobinuria</condition>
  <arm_group>
    <arm_group_label>Arm A (Crovalimab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adult Participants will receive an initial intravenous (IV) loading dose on Week 1 Day 1, followed by 4 weekly crovalimab subcutaneous (SC) doses on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter, for a total of at least 24 weeks of study treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (Eculizumab)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Adult Participants will receive initial IV weekly doses for 4 weeks which will be followed by Q2W (every 2 weeks) IV administrations starting on Week 5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C (Crovalimab) (Exploratory)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paediatric participants will receive a loading series of Crovalimab comprised of an IV dose on Week 1 Day 1, followed by weekly crovalimab SC doses for 4 weeks on Week 1 (Day 2) then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will be administered Q4W thereafter. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crovalimab</intervention_name>
    <description>Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 and 100kg) or 1500 mg IV (for participants with body weight &gt;=100kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100kg) or 1020 mg SC (for participants with body weight &gt;=100kg). Dosing schedule will be as described above.</description>
    <arm_group_label>Arm A (Crovalimab)</arm_group_label>
    <arm_group_label>Arm C (Crovalimab) (Exploratory)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eculizumab</intervention_name>
    <description>Eculizumab will be administered at a dose of 600 mg for the first 4 weeks, followed by maintenance doses of 900 mg starting on Week 5, as per the dosing schedule described above.</description>
    <arm_group_label>Arm B (Eculizumab)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body weight &gt;= 40 kg at screening.&#xD;
&#xD;
          -  Willingness and ability to comply with all study visits and procedures.&#xD;
&#xD;
          -  Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.&#xD;
&#xD;
          -  LDH level &gt;= 2x ULN at screening (as per local assessment).&#xD;
&#xD;
          -  Vaccination against Neisseria meningitidis serotypes A, C, W, &lt; 3 years prior to&#xD;
             initiation of study treatment; or, if not previously done, vaccination administered no&#xD;
             later than one week after the first drug administration.&#xD;
&#xD;
          -  Women of childbearing potential: agreement to remain abstinent or use contraception&#xD;
             during the treatment period and for 10.5 months after the final dose of crovalimab or&#xD;
             for 3 months after the final dose of eculizumab (or longer if required by the local&#xD;
             product label).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or previous treatment with a complement inhibitor.&#xD;
&#xD;
          -  History of allogeneic bone marrow transplantation.&#xD;
&#xD;
          -  History of Neisseria meningitidis infection within 6 months prior to screening and up&#xD;
             to first study drug administration.&#xD;
&#xD;
          -  History of myelodysplastic syndrome with Revised International Prognostic Scoring&#xD;
             System (IPSS-R) prognostic risk categories of intermediate, high and very high.&#xD;
&#xD;
          -  Pregnant or breastfeeding, or intending to become pregnant during the study, within&#xD;
             10.5 months after the final dose of crovalimab, or 3 months after the final dose of&#xD;
             eculizumab (or longer if required by the local product label).&#xD;
&#xD;
          -  Participation in another interventional treatment study with an investigational agent&#xD;
             or use of any experimental therapy within 28 days of screening or within 5 half-lives&#xD;
             of that investigational product, whichever is greater.&#xD;
&#xD;
          -  Concurrent disease, treatment, procedure or surgery, or abnormality in clinical&#xD;
             laboratory tests that could interfere with the conduct of the study, may pose any&#xD;
             additional risk for the participant, or would, in the opinion of the Investigator,&#xD;
             preclude the participant's safe participation in and completion of the study.&#xD;
&#xD;
          -  Splenectomy &lt; 6 months before screening.&#xD;
&#xD;
          -  Positive for Active Hepatitis B and C infection (HBV/HCV).&#xD;
&#xD;
          -  History of or ongoing cryoglobulinemia at screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Organizacion Medica de Investigacion (OMI)</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1015ABO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integrado de Oncologia de Curitiba</name>
      <address>
        <city>Curitiba</city>
        <state>PR</state>
        <zip>80810-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre X</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>*X*CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia</name>
      <address>
        <city>Santo André</city>
        <state>SP</state>
        <zip>09060-650</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beneficencia Portuguesa de Sao Paulo</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01321-00</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing City</city>
        <zip>100032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nanfang Hospital, Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Zhejiang University</name>
      <address>
        <city>Hangzhou City</city>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangsu Province Hospital</name>
      <address>
        <city>Nanjing</city>
        <zip>210008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affiliated Hospital of Nantong University; Nephrology</name>
      <address>
        <city>Nantong City</city>
        <zip>226001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huashan Hospital, Fudan University</name>
      <address>
        <city>Shanghai City</city>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Union Hospital Tongji Medical College Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan City</city>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Claude Huriez - CHU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinkm</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital of Thessaloniki G. Papanikolaou</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Chinese University of Hong Kong; Department of Medicine &amp; Therapeutics</name>
      <address>
        <city>Shatin</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sapporo Medical University Hospital</name>
      <address>
        <city>Hokkaido</city>
        <zip>060-8543</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Tsukuba Hospital</name>
      <address>
        <city>Ibaraki</city>
        <zip>305-8576</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NTT Medical Center Tokyo</name>
      <address>
        <city>Tokyo</city>
        <zip>141-8625</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Medical University Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>160-0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vilnius University Hospital Santariskiu Clinics, Public Institution; Cardiology</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Tengku Ampuan Afzan</name>
      <address>
        <city>Kuantan</city>
        <state>Pahang</state>
        <zip>25100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Raja Permaisuri Bainun</name>
      <address>
        <city>Ipoh</city>
        <state>Perak</state>
        <zip>30990</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ampang</name>
      <address>
        <city>Ampang</city>
        <zip>68000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pulau Pinang</name>
      <address>
        <city>Penang</city>
        <zip>10990</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Global Trial Research Center S.A. de C.V.</name>
      <address>
        <city>Monterrey</city>
        <state>Nuevo LEON</state>
        <zip>64718</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran</name>
      <address>
        <city>Mexico</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC, Locatie AMC</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Mediatrix Medical Center</name>
      <address>
        <city>Lipa City</city>
        <zip>4217</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philippine General Hospital; Pulmonary Medicine</name>
      <address>
        <city>Manila</city>
        <zip>1000</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Lukes Medical Center</name>
      <address>
        <city>Quezon City</city>
        <zip>1102</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki nr2 im. dr J. Biziela</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii</name>
      <address>
        <city>Gdansk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Szpital Kliniczny nr 1</name>
      <address>
        <city>Lublin</city>
        <zip>20-081</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne Pratia Poznan</name>
      <address>
        <city>Skórzewo</city>
        <zip>60-185</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MTZ Clinical Research Powered by Pratia</name>
      <address>
        <city>Warszawa</city>
        <zip>02-172</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar do Baixo Vouga E.P.E. - Hospital de Aveiro</name>
      <address>
        <city>Aveiro</city>
        <zip>3814-501</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar de Lisboa Central - Hospital D. Estefânia; Pediatrics</name>
      <address>
        <city>Lisboa</city>
        <zip>1169-045</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.</name>
      <address>
        <city>Lisbon</city>
        <zip>1050-034</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar do Porto - Hospital de Santo António</name>
      <address>
        <city>Porto</city>
        <zip>4099-001</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Universitar de Urgenta Bucuresti</name>
      <address>
        <city>Bucharest</city>
        <zip>11172</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spitalul Clinic Municipal Filantropia Craiova</name>
      <address>
        <city>Craiova</city>
        <zip>200143</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>117599</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital; Department of Haematology</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Badalona - Hospital Universitari Germans Trias i Pujol; Hematologia Clinica</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Gran Canaria Doctor Negrín; Servicio de Hematología</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <state>LAS Palmas</state>
        <zip>35010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Basurto</name>
      <address>
        <city>Bilbao</city>
        <state>Vizcaya</state>
        <zip>48013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Pedro de Alcantara</name>
      <address>
        <city>Caceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akademiska Sjukhuset</name>
      <address>
        <city>Uppsala</city>
        <zip>751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Medical Foundation - Kaohsiung; Oncology</name>
      <address>
        <city>Kaohisung</city>
        <zip>833</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan Universtiy Hospital; Division of Hematology</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Chulalongkorn Memorial Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siriraj Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maharaj Nakorn Chiang Mai Hospital</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ondokuz Mayis Univ. Med. Fac.</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center OK!Clinic+</name>
      <address>
        <city>Kyiv</city>
        <state>KIEV Governorate</state>
        <zip>02091</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mykolayiv Regional Hospital</name>
      <address>
        <city>Mykolaiv</city>
        <state>KIEV Governorate</state>
        <zip>54058</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James University Hospital</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings College Hospital; Kings Clinical Research Facility</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Brazil</country>
    <country>China</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hong Kong</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Philippines</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Romania</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czechia</country>
    <country>Estonia</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Peru</country>
    <country>Saudi Arabia</country>
    <country>South Africa</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemoglobinuria</mesh_term>
    <mesh_term>Hemoglobinuria, Paroxysmal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eculizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04434092
org study id: BO42162
secondary id: 2019-004931-21
nct id: NCT04434092
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A study designed to evaluate the non-inferiority of crovalimab compared with eculizumab in
      participants with PNH who have not been previously treated with complement inhibitor therapy.
      This study will enroll approximately 200 participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants who achieve Transfusion Avoidance (TA)
time frame: Baseline through Week 25
description: TA is defined as patients who are packed Red Blood Cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines.
measure: Percentage of Participants with hemolysis control
time frame: Week 5 through Week 25
description: Measured by LDH =< 1.5 x ULN (as measured at the central laboratory).
measure: Percentage of Participants with Breakthrough Hemolysis (BTH)
time frame: Baseline through Week 25
description: BTH is defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin < 10 g/dL], a major adverse vascular event [MAVE; including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH >= 2 x ULN after prior reduction of LDH to =<1.5 x ULN on treatment.
measure: Percentage of Participants with Stabilization of Hemoglobin
time frame: Baseline through Week 25
description: Stabilized hemoglobin is defined as avoidance of a >= 2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion.
measure: Mean Change in Fatigue
time frame: Baseline up to Week 25
description: Assessed by the FACIT-Fatigue Questionnaire.
measure: Percentage of Participants with Adverse Events (AEs)
time frame: Up to 7 years
description: Determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.
measure: Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity and Infections (including meningococcal meningitis)
time frame: Up to 7 years
measure: Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation
time frame: Up to 7 years
measure: Percentage of Participants with clinical manifestations of Drug-Target-Drug Complex (DTDC) formation amongst those participants who switched to crovalimab treatment from eculizumab treatment
time frame: Up to 6.5 years
measure: Serum concentrations of crovalimab and eculizumab over time
time frame: Up to 6.5 years
measure: Percentage of Participants with Anti-Crovalimab Antibodies
time frame: Up to 6.5 years
measure: Change in PD biomarkers including complement activity (CH50) over time
time frame: Up to 6.5 years
description: Assessed by a Liposome Immunoassay (LIA) and total C5 concentration
measure: Change over time in free C5 concentration in crovalimab-treated participants
time frame: Up to 6.5 years
measure: Observed Value in Reticulocyte Count (count/mL)
time frame: Up to 6.5 years
measure: Observed Value in Free Hemoglobin and Haptoglobin (mg/dL)
time frame: Up to 6.5 years
measure: Change in Reticulocyte Count (count/mL)
time frame: Baseline up to Week 25
measure: Change in Free Hemoglobin and Haptoglobin (mg/dL)
time frame: Baseline up to Week 25
arm group label: Arm A (Crovalimab)
arm group type: Experimental
description: Adult Participants will receive an initial intravenous (IV) loading dose on Week 1 Day 1, followed by 4 weekly crovalimab subcutaneous (SC) doses on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance dosing will begin at Week 5 and will continue Q4W (every 4 weeks) thereafter, for a total of at least 24 weeks of study treatment.
arm group label: Arm B (Eculizumab)
arm group type: Active Comparator
description: Adult Participants will receive initial IV weekly doses for 4 weeks which will be followed by Q2W (every 2 weeks) IV administrations starting on Week 5.
arm group label: Arm C (Crovalimab) (Exploratory)
arm group type: Experimental
description: Paediatric participants will receive a loading series of Crovalimab comprised of an IV dose on Week 1 Day 1, followed by weekly crovalimab SC doses for 4 weeks on Week 1 (Day 2) then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will be administered Q4W thereafter. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.
intervention type: Drug
intervention name: Crovalimab
description: Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 and 100kg) or 1500 mg IV (for participants with body weight >=100kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100kg) or 1020 mg SC (for participants with body weight >=100kg). Dosing schedule will be as described above.
arm group label: Arm A (Crovalimab)
arm group label: Arm C (Crovalimab) (Exploratory)
intervention type: Drug
intervention name: Eculizumab
description: Eculizumab will be administered at a dose of 600 mg for the first 4 weeks, followed by maintenance doses of 900 mg starting on Week 5, as per the dosing schedule described above.
arm group label: Arm B (Eculizumab)
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Argentina
country: Australia
country: Brazil
country: China
country: France
country: Germany
country: Greece
country: Hong Kong
country: Japan
country: Korea, Republic of
country: Lithuania
country: Malaysia
country: Mexico
country: Netherlands
country: Philippines
country: Poland
country: Portugal
country: Romania
country: Singapore
country: Spain
country: Sweden
country: Taiwan
country: Thailand
country: Turkey
country: Ukraine
country: United Kingdom
country: Belgium
country: Canada
country: Chile
country: Colombia
country: Czechia
country: Estonia
country: Hungary
country: Ireland
country: Israel
country: Italy
country: Peru
country: Saudi Arabia
country: South Africa
country: United States
responsible party type: Sponsor
mesh term: Hemoglobinuria
mesh term: Hemoglobinuria, Paroxysmal
mesh term: Eculizumab
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).