<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/NCT04431726</url>
  </required_header>
  <id_info>
    <org_study_id>MO41787</org_study_id>
    <secondary_id>2020-001733-12</secondary_id>
    <nct_id>NCT04431726</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Participants From Birth to 12 Months of Age With Hemophilia A Without Inhibitors</brief_title>
  <acronym>HAVEN 7</acronym>
  <official_title>A Phase IIIb, Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients From Birth to 12 Months of Age With Hemophilia A Without Inhibitors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a Phase IIIb, multicenter, open-label, single-arm study of prophylactic emicizumab in&#xD;
      previously untreated and minimally treated patients at study enrollment from birth to ≤12&#xD;
      months of age with severe hemophilia A (intrinsic factor VIII [FVIII] level &lt;1%) without&#xD;
      FVIII inhibitors. The study is designed to evaluate the efficacy, safety, pharmacokinetics,&#xD;
      and pharmacodynamics of emicizumab administered at 3 milligrams per kilogram of body weight&#xD;
      (mg/kg) once every 2 weeks (Q2W) for 52 weeks. After 1 year of treatment, participants will&#xD;
      continue to receive emicizumab (1.5 mg/kg once every week [QW], 3 mg/kg Q2W or 6 mg/kg once&#xD;
      every 4 weeks [Q4W]) over a 7-year long-term follow-up period under this study frame.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 4, 2021</start_date>
  <completion_date type="Anticipated">May 20, 2030</completion_date>
  <primary_completion_date type="Actual">May 22, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Model-Based Annualized Bleeding Rate for Treated Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Calculated Annualized Bleeding Rate for Treated Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Calculated Annualized Bleeding Rate for Treated Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Model-Based Annualized Bleeding Rate for All Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Calculated Annualized Bleeding Rate for All Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Calculated Annualized Bleeding Rate for All Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Model-Based Annualized Bleeding Rate for Treated Joint Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds</measure>
    <time_frame>From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemophilia Joint Health Score (HJHS) Total Score at Specified Timepoints During the Long-Term Follow-Up Period</measure>
    <time_frame>At 4, 5, 6, 7, and 8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnetic Resonance Imaging (MRI) Score of Specific Joints at Specified Timepoints During the Long-Term Follow-Up Period</measure>
    <time_frame>At 5 and 8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of Adverse Events, with Severity Determined According to World Health Organization (WHO) Toxicity Grading Scale</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Thromboembolic Events</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Thrombotic Microangiopathy</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of of Injection Site Reactions, with Severity Determined According to WHO Toxicity Grading Scale</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Events</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events Leading to Study Drug Discontinuation</measure>
    <time_frame>From Baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Laboratory Abnormalities in Serum Chemistry and Hematology Tests</measure>
    <time_frame>Baseline, Weeks 4, 13, 21, 29, 37, 45, and 53</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Pulse Rate Over Time</measure>
    <time_frame>Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Respiratory Rate Over Time</measure>
    <time_frame>Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Body Temperature Over Time</measure>
    <time_frame>Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Systolic Blood Pressure Over Time</measure>
    <time_frame>Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Diastolic Blood Pressure Over Time</measure>
    <time_frame>Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Trough Concentrations (Ctrough) of Emicizumab</measure>
    <time_frame>Predose at Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Anti-Emicizumab Antibodies</measure>
    <time_frame>Weeks 1, 5, 17, 29, 41, and 53, and thereafter as clinically indicated until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of De Novo Development of Factor VIII Inhibitors</measure>
    <time_frame>As clinically indicated from baseline until study completion (up to 8 years)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Severe Hemophilia A</condition>
  <arm_group>
    <arm_group_label>Emicizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Emicizumab</intervention_name>
    <description>Initially, all participants will receive 4 loading doses of 3 milligrams per kilogram (mg/kg) emicizumab subcutaneously (SC) once every week (QW) for 4 weeks followed by the maintenance dosing regimen 3 mg/kg emicizumab SC once every 2 weeks (Q2W) for a total of 52 weeks. Starting from Week 17 of treatment, individual participants may have their dose up-titrated to 3 mg/kg SC QW if they experience suboptimal bleeding control.&#xD;
At the Week 53 clinic visit following consultation with the treating physician, parents/caregivers may elect for their child to continue with the maintenance 3-mg/kg SC Q2W dosing regimen or to switch to the maintenance 1.5-mg/kg SC QW or 6-mg/kg SC once every 4 weeks (Q4W) dosing regimen for the subsequent 7-year long-term follow-up period.&#xD;
During the study, participants will be treated with emicizumab until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria specified in the protocol, whichever occurs first.</description>
    <arm_group_label>Emicizumab</arm_group_label>
    <other_name>Hemlibra</other_name>
    <other_name>RO5534262</other_name>
    <other_name>RG6013</other_name>
    <other_name>ACE910</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age from birth to ≤12 months at time of informed consent&#xD;
&#xD;
          -  Body weight ≥3 kilograms (kg) at time of informed consent. Patients with a lower body&#xD;
             weight can be enrolled after they have reached a body weight of 3 kg. Premature babies&#xD;
             (gestational age &lt;38 weeks) may be enrolled as long as they have reached a body weight&#xD;
             of 3 kg. For premature babies, the corrected gestational age should be reported.&#xD;
&#xD;
          -  Mandatory receipt of vitamin K prophylaxis according to local standard practice&#xD;
&#xD;
          -  Diagnosis of severe congenital hemophilia A (intrinsic FVIII level &lt;1%)&#xD;
&#xD;
          -  A negative test for FVIII inhibitor (i.e., &lt;0.6 Bethesda units [BU]/mL) locally&#xD;
             assessed during the 2-week screening period&#xD;
&#xD;
          -  No history of documented FVIII inhibitor (i.e., &lt;0.6 BU/mL), FVIII drug-elimination&#xD;
             half-life &lt;6 hours, or FVIII recovery &lt;66%&#xD;
&#xD;
          -  Previously untreated patients or minimally treated patients (i.e., up to 5 days of&#xD;
             exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant&#xD;
             FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)&#xD;
&#xD;
          -  Documentation of the details of the hemophilia-related treatments received since birth&#xD;
&#xD;
          -  Documentation of the details of the bleeding episodes since birth&#xD;
&#xD;
          -  For patients from birth to &lt;3 months of age at the time of study entry: no evidence of&#xD;
             active intracranial hemorrhage, as confirmed by a negative cranial ultrasound at&#xD;
             screening irrespective of delivery mode&#xD;
&#xD;
          -  Adequate hematologic, hepatic, and renal function, as defined in the protocol&#xD;
&#xD;
          -  For parents/caregivers: willingness and ability to comply with the study protocol&#xD;
             requirements, scheduled visits, treatment plans, laboratory tests, completion of&#xD;
             applicable questionnaires, and other study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inherited or acquired bleeding disorder other than severe hemophilia A&#xD;
&#xD;
          -  Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use&#xD;
             during the study&#xD;
&#xD;
          -  Receipt of any of the following: Prior use of emicizumab prophylaxis including&#xD;
             investigational or commercial emicizumab; An investigational drug to treat or reduce&#xD;
             the risk of hemophilic bleeds within 5 drug-elimination half-lives of last drug&#xD;
             administration; A non-hemophilia-related investigational drug within the last 30 days&#xD;
             or 5 drug-elimination half-lives, whichever is shorter; An investigational drug&#xD;
             concurrently&#xD;
&#xD;
          -  Current active severe bleed, such as intracranial hemorrhage&#xD;
&#xD;
          -  Planned surgery (excluding minor procedures, e.g., circumcision, CVAD placement)&#xD;
             during the study&#xD;
&#xD;
          -  History of clinically significant hypersensitivity associated with monoclonal antibody&#xD;
             therapies or components of the emicizumab injection&#xD;
&#xD;
          -  Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a&#xD;
             previous medical or family history of TMA, such as thrombotic thrombocytopenic&#xD;
             purpura, atypical hemolytic uremic syndrome) in the investigator's judgment&#xD;
&#xD;
          -  Previous or current treatment for thromboembolic disease (with the exception of&#xD;
             previous catheter-associated thrombosis in patients for whom anti-thrombotic treatment&#xD;
             is not currently ongoing) or signs of thromboembolic disease&#xD;
&#xD;
          -  Any hereditary or acquired maternal condition that may predispose the patient to&#xD;
             thrombotic events (e.g., inherited thrombophilias antiphospholipid syndrome)&#xD;
&#xD;
          -  Other diseases (e.g., certain autoimmune diseases) that may increase risk of bleeding&#xD;
             or thrombosis&#xD;
&#xD;
          -  Known infection with HIV, hepatitis B virus, or hepatitis C virus&#xD;
&#xD;
          -  Serious infection requiring antibiotics or antiviral treatments within 14 days prior&#xD;
             to screening&#xD;
&#xD;
          -  Concurrent disease, treatment, abnormality in clinical laboratory tests, vital signs&#xD;
             measurements, or physical examination findings that could interfere with the conduct&#xD;
             of the study or that would, in the opinion of the investigator or Sponsor, preclude&#xD;
             the patient's safe participation in and completion of the study or interpretation of&#xD;
             the study results&#xD;
&#xD;
          -  Unwillingness of the parent or caregiver to allow receipt of blood or blood products,&#xD;
             or any standard-of-care treatment for a life-threatening condition&#xD;
&#xD;
          -  Any other medical, social, or other condition that may prevent adequate compliance&#xD;
             with the study protocol in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Months</minimum_age>
    <maximum_age>12 Months</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>Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver, Children's Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane University Health Sciences Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112-2632</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-0934</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital at Westmead</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Children's Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Perth Children's Hospital</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Wien; Univ. Klinik für Kinder und Jugendheilkunde</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires St-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clínicas Faculdades Médicas de Ribeirão Preto</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>SP</state>
        <zip>14051-140</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Eastern Ontario</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Necker Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hämophilie-Zentrum Rhein Main GmbH</name>
      <address>
        <city>Mörfelden-Walldorf</city>
        <zip>64546</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center - National Hemophilia Center</name>
      <address>
        <city>Tel Hashomer</city>
        <zip>5262100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AORN Santobono Pausilipon; UOC di Ematologia ? Centro Emofilia e Trombosi</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU di Parma; Dip Emergenza-Urgenza Centro Riferimento Regionale per l'emofilia</name>
      <address>
        <city>Parma</city>
        <state>Emilia-Romagna</state>
        <zip>43126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi &quot;Angelo Bianchi e Bonomi&quot;</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Careggi; SOD Malattie Emorragiche</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center</name>
      <address>
        <city>Johannesburg</city>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Deu; Servicio de Oncologia y Hematologia</name>
      <address>
        <city>Esplugues de Llobregat</city>
        <state>Barcelona</state>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario la Paz; Servicio de Hematologia</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio; Servicio de Hematologia</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adana Acibadem Hospital; Pediatric Hematology</name>
      <address>
        <city>Adana</city>
        <zip>01130</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe University Medical Faculty; Hacettepe University Medical Faculty</name>
      <address>
        <city>Ankara</city>
        <zip>06100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ege University, School of Medicine; Pediatrics Department</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</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>Arthur Bloom Haemophilia Centre</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal London Hospital</name>
      <address>
        <city>London</city>
        <zip>E1 1FR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Netherlands</country>
    <country>Switzerland</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe hemophilia A Without Factor VIII Inhibitors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).&#xD;
For further details on Roche's Global Policy on Sharing of Clinical Study 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/NCT04431726
org study id: MO41787
secondary id: 2020-001733-12
nct id: NCT04431726
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase IIIb, multicenter, open-label, single-arm study of prophylactic emicizumab in
      previously untreated and minimally treated patients at study enrollment from birth to ≤12
      months of age with severe hemophilia A (intrinsic factor VIII [FVIII] level <1%) without
      FVIII inhibitors. The study is designed to evaluate the efficacy, safety, pharmacokinetics,
      and pharmacodynamics of emicizumab administered at 3 milligrams per kilogram of body weight
      (mg/kg) once every 2 weeks (Q2W) for 52 weeks. After 1 year of treatment, participants will
      continue to receive emicizumab (1.5 mg/kg once every week [QW], 3 mg/kg Q2W or 6 mg/kg once
      every 4 weeks [Q4W]) over a 7-year long-term follow-up period under this study frame.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Model-Based Annualized Bleeding Rate for Treated Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Median Calculated Annualized Bleeding Rate for Treated Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Mean Calculated Annualized Bleeding Rate for Treated Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Model-Based Annualized Bleeding Rate for All Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Median Calculated Annualized Bleeding Rate for All Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Mean Calculated Annualized Bleeding Rate for All Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
time frame: From Baseline to 52 weeks, and during 7-year long-term follow-up period until study completion (up to 8 years)
measure: Hemophilia Joint Health Score (HJHS) Total Score at Specified Timepoints During the Long-Term Follow-Up Period
time frame: At 4, 5, 6, 7, and 8 years
measure: Magnetic Resonance Imaging (MRI) Score of Specific Joints at Specified Timepoints During the Long-Term Follow-Up Period
time frame: At 5 and 8 years
measure: Incidence and Severity of Adverse Events, with Severity Determined According to World Health Organization (WHO) Toxicity Grading Scale
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence of Thromboembolic Events
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence of Thrombotic Microangiopathy
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence and Severity of of Injection Site Reactions, with Severity Determined According to WHO Toxicity Grading Scale
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence of Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Events
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence of Adverse Events Leading to Study Drug Discontinuation
time frame: From Baseline until study completion (up to 8 years)
measure: Incidence of Laboratory Abnormalities in Serum Chemistry and Hematology Tests
time frame: Baseline, Weeks 4, 13, 21, 29, 37, 45, and 53
measure: Change from Baseline in Pulse Rate Over Time
time frame: Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
measure: Change from Baseline in Respiratory Rate Over Time
time frame: Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
measure: Change from Baseline in Body Temperature Over Time
time frame: Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
measure: Change from Baseline in Systolic Blood Pressure Over Time
time frame: Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
measure: Change from Baseline in Diastolic Blood Pressure Over Time
time frame: Baseline, Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53, and annually during the 7-year follow-up period until study completion (up to 8 years)
measure: Plasma Trough Concentrations (Ctrough) of Emicizumab
time frame: Predose at Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, and 53
measure: Incidence of Anti-Emicizumab Antibodies
time frame: Weeks 1, 5, 17, 29, 41, and 53, and thereafter as clinically indicated until study completion (up to 8 years)
measure: Incidence of De Novo Development of Factor VIII Inhibitors
time frame: As clinically indicated from baseline until study completion (up to 8 years)
arm group label: Emicizumab
arm group type: Experimental
intervention type: Drug
intervention name: Emicizumab
description: Initially, all participants will receive 4 loading doses of 3 milligrams per kilogram (mg/kg) emicizumab subcutaneously (SC) once every week (QW) for 4 weeks followed by the maintenance dosing regimen 3 mg/kg emicizumab SC once every 2 weeks (Q2W) for a total of 52 weeks. Starting from Week 17 of treatment, individual participants may have their dose up-titrated to 3 mg/kg SC QW if they experience suboptimal bleeding control.
At the Week 53 clinic visit following consultation with the treating physician, parents/caregivers may elect for their child to continue with the maintenance 3-mg/kg SC Q2W dosing regimen or to switch to the maintenance 1.5-mg/kg SC QW or 6-mg/kg SC once every 4 weeks (Q4W) dosing regimen for the subsequent 7-year long-term follow-up period.
During the study, participants will be treated with emicizumab until unacceptable toxicity, discontinuation from the study due to any cause, or other criteria specified in the protocol, whichever occurs first.
arm group label: Emicizumab
other name: Hemlibra
other name: RO5534262
other name: RG6013
other name: ACE910
criteria: 
gender: All
minimum age: 0 Months
maximum age: 12 Months
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Australia
country: Austria
country: Belgium
country: Brazil
country: Canada
country: France
country: Germany
country: Israel
country: Italy
country: South Africa
country: Spain
country: Turkey
country: United Kingdom
country: United States
country: Netherlands
country: Switzerland
responsible party type: Sponsor
mesh term: Hemophilia A
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the 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 Sharing of Clinical Study 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).