<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/NCT02234323</url>
  </required_header>
  <id_info>
    <org_study_id>997HA306</org_study_id>
    <secondary_id>2013-005512-10</secondary_id>
    <nct_id>NCT02234323</nct_id>
  </id_info>
  <brief_title>An Open Label Study to Determine the Safety and Efficacy of Replacement Factor VIII Protein (Known as rFVIIIFc) in Previously Untreated Males With Severe Hemophilia A</brief_title>
  <official_title>An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in the Prevention and Treatment of Bleeding in Previously Untreated Patients With Severe Hemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioverativ, a Sanofi company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swedish Orphan Biovitrum</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study was to evaluate the safety of rFVIIIFc (BIIB031) in&#xD;
      previously untreated participants (PUPs) with severe hemophilia A. The secondary objectives&#xD;
      were to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding&#xD;
      episodes in PUPs, to evaluate rFVIIIFc consumption for the prevention and treatment of&#xD;
      bleeding episodes in PUPs, and to describe experience with the use of rFVIIIFc for immune&#xD;
      tolerance induction (ITI) in participants with inhibitors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 12, 2015</start_date>
  <completion_date type="Actual">September 23, 2019</completion_date>
  <primary_completion_date type="Actual">September 23, 2019</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>Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>A positive/confirmed inhibitor result occurs when a participant has a value &gt;=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected &gt;=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached &gt;=10 EDs and had &gt;=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received &gt;=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent &quot;strenuous&quot; activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than [&gt;]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized Number of Spontaneous Joint Bleeding Episodes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent &quot;strenuous&quot; activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (&gt; 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Exposure Days (EDs)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in rFVIIIFc Incremental Recovery (IR)</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120</time_frame>
    <description>Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (&lt;)0.5 IU/dL was set to 0 IU/dL for calculation of IR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Response to Immune Tolerance Induction (ITI)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR &gt;=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life &gt;=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Hemophilia A</condition>
  <arm_group>
    <arm_group_label>rFVIIIFc</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (&gt;=) 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 Bethesda Units per milliliter [BU/mL]) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rFVIIIFc</intervention_name>
    <description>Administered as specified in arm description</description>
    <arm_group_label>rFVIIIFc</arm_group_label>
    <other_name>Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]</other_name>
    <other_name>Fc fusion protein</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Ability of the participant's legally authorized representative (e.g. their parent or&#xD;
             legal guardian) to understand the purpose and risks of the study and provide signed&#xD;
             and dated informed consent and authorization to use confidential health information in&#xD;
             accordance with national and local participant privacy regulations.&#xD;
&#xD;
          -  Weight &gt;=3.5 kg at the time of screening.&#xD;
&#xD;
          -  Severe hemophilia A defined as less than (&lt;) 1 IU/dL (&lt;1%) endogenous FVIII documented&#xD;
             in the medical record or as tested during the Screening Period.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any exposure to blood components, factor VIII replacement products, including&#xD;
             commercially available rFVIIIFc at any time prior to or during screening.&#xD;
&#xD;
          -  History of positive inhibitor testing. A prior history of inhibitors was defined based&#xD;
             on a patient's historical positive inhibitor test using the local laboratory Bethesda&#xD;
             value for a positive inhibitor test (ie, equal to or above lower level of detection).&#xD;
&#xD;
          -  History of hypersensitivity reactions associated with any rFVIIIFc administration.&#xD;
&#xD;
          -  Other coagulation disorder(s) in addition to hemophilia A.&#xD;
&#xD;
          -  Any concurrent clinically significant major disease that, in the opinion of the&#xD;
             Investigator, would make the participant unsuitable for enrollment.&#xD;
&#xD;
          -  Current systemic treatment with chemotherapy and/or other immunosuppressant drugs.&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>5 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brewer</city>
        <state>Maine</state>
        <zip>04412</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>East Lansing</city>
        <state>Michigan</state>
        <zip>48823</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brisbane</city>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parkville</city>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Perth</city>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Westmead</city>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Campinas</city>
        <zip>13083-878</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Canoas</city>
        <zip>92425-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ribeirão Preto</city>
        <zip>14048-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20211-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>São Paulo</city>
        <zip>01227-200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hamilton</city>
        <zip>L8S 4K1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>N6A 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caen cedex 9</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Le Kremlin Bicêtre cedex</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lille Cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nantes Cedex 1</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toulouse cedex</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tours cedex 9</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Duesseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hannöver</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dublin</city>
        <zip>D12 N512</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vicenza</city>
        <state>VI</state>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bari</city>
        <zip>70123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Florence</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Genova</city>
        <zip>16148</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Napoli</city>
        <zip>80123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rome</city>
        <zip>161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rome</city>
        <zip>165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leiden</city>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Auckland</city>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Gdansk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kraków</city>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lublin</city>
        <zip>20-093</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>02-091</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Stockholm</city>
        <zip>171 76</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Basingstoke</city>
        <state>Hampshire</state>
        <zip>RG24 9NA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Whitechapel</city>
        <state>London</state>
        <zip>E1 1BB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>WC1N3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Denmark</country>
  </removed_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>July 28, 2020</results_first_submitted>
  <results_first_submitted_qc>July 28, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 13, 2020</results_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prophylaxis treatment</keyword>
  <keyword>Hemophilia A</keyword>
  <keyword>Hemophilia</keyword>
  <keyword>episodic treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Factor VIII</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT02234323/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT02234323/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 44 active centers in 13 countries between 12-Jan-2015 to 23-Sep-2019.</recruitment_details>
      <pre_assignment_details>110 participants screened, 108 enrolled, 103 received drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
          <description>Participants were to receive rFVIIIFc as follows -Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3-5 day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 Bethesda Units per milliliter [BU/mL]) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>All Enrolled</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="103">These participants received at least one dose of study drug.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not Treated: Completed study in database</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not Treated:Consent withdrawn by subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not Treated: Exceeded lab value limit</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>All Treated</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="103"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Episodic Treatment Regimen</title>
              <participants_list>
                <participants group_id="P1" count="81">Participants were treated in more than one regimen and counted in all categories wherever applicable</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Prophylactic Treatment Regimen</title>
              <participants_list>
                <participants group_id="P1" count="89">69 participants among the 81 who started in episodic regimen, switched to the prophylactic regimen.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Immune Tolerance Induction (ITI)</title>
              <participants_list>
                <participants group_id="P1" count="15">1/81 on episodic and 14/89 on prophylactic regimen had inhibitors and were switched directly to ITI.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Exceeded lab value limit</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety analysis set was defined as all participants who received at least 1 dose of rFVIIIFc.</population>
      <group_list>
        <group group_id="B1">
          <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
          <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="103"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.58" lower_limit="0.02" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African-American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not reported due to confidentiality regulations</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay</title>
        <description>A positive/confirmed inhibitor result occurs when a participant has a value &gt;=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected &gt;=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached &gt;=10 EDs and had &gt;=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received &gt;=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Safety analysis set participants who 1) reached &gt;=10 EDs and had &gt;=1 inhibitor test performed at &gt;=10 EDs or who had inhibitor or 2) did not develop inhibitor but reached &gt;=10 EDs or 3) developed an inhibitor following the initial rFVIIIFc administration.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR (Prophylaxis regimen): rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay</title>
          <description>A positive/confirmed inhibitor result occurs when a participant has a value &gt;=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected &gt;=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached &gt;=10 EDs and had &gt;=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received &gt;=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.</description>
          <population>Safety analysis set participants who 1) reached &gt;=10 EDs and had &gt;=1 inhibitor test performed at &gt;=10 EDs or who had inhibitor or 2) did not develop inhibitor but reached &gt;=10 EDs or 3) developed an inhibitor following the initial rFVIIIFc administration.</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="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.11" lower_limit="21.77" upper_limit="41.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])</title>
        <description>ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent &quot;strenuous&quot; activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than [&gt;]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on Full Analysis Set (FAS) participants within the EP. FAS included all enrolled participants with &gt;=1 dose of study treatment. Here, number analyzed signifies number of FAS participants analyzed in each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])</title>
          <description>ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent &quot;strenuous&quot; activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than [&gt;]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on Full Analysis Set (FAS) participants within the EP. FAS included all enrolled participants with &gt;=1 dose of study treatment. Here, number analyzed signifies number of FAS participants analyzed in each treatment regimen.</population>
          <units>episodes per participant per year</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.24" lower_limit="0.0" upper_limit="39.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.49" lower_limit="0.0" upper_limit="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Number of Spontaneous Joint Bleeding Episodes</title>
        <description>Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent &quot;strenuous&quot; activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (&gt; 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis was performed on FAS which included participants within EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Number of Spontaneous Joint Bleeding Episodes</title>
          <description>Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent &quot;strenuous&quot; activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (&gt; 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis was performed on FAS which included participants within EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
          <units>episodes per participant per year</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale</title>
        <description>Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on FAS participants within the EP and based on all injections. Here, number analyzed signifies number of responses to injections reported for each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale</title>
          <description>Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on FAS participants within the EP and based on all injections. Here, number analyzed signifies number of responses to injections reported for each treatment regimen.</population>
          <units>responses to injections</units>
          <param>Count of Units</param>
          <units_analyzed>responses to injections</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>responses to injections</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="579"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Regimen</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>responses to injections</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="238"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Excellent or Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="102"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Response not provided</title>
                  <measurement_list>
                    <measurement group_id="O1" value="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Regimen</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>responses to injections</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="293"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Excellent or Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="163"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Response not provided</title>
                  <measurement_list>
                    <measurement group_id="O1" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Regimen</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>responses to injections</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Excellent or Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Response not provided</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Exposure Days (EDs)</title>
        <description>An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on safety analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Exposure Days (EDs)</title>
          <description>An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.</description>
          <population>Analysis performed on safety analysis set.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="0" upper_limit="649"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</title>
        <description>Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</title>
          <description>Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
          <units>IU per kilogram per participant per year</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="197.6" lower_limit="0" upper_limit="3177"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5384.4" lower_limit="0" upper_limit="40126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67310.0" lower_limit="33323" upper_limit="78871"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode</title>
        <description>Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode</title>
          <description>Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (&gt;28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
          <units>injections</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode</title>
        <description>The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode</title>
          <description>The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on FAS participants within the EP. Here, number analyzed signifies number of FAS participants who were analyzed in each treatment regimen.</population>
          <units>IU/kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Episodic Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.45" lower_limit="19.2" upper_limit="106.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prophylaxis Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="89"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.08" lower_limit="17.9" upper_limit="144.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ITI Treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="189.44" lower_limit="76.9" upper_limit="250.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in rFVIIIFc Incremental Recovery (IR)</title>
        <description>Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (&lt;)0.5 IU/dL was set to 0 IU/dL for calculation of IR.</description>
        <time_frame>Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120</time_frame>
        <population>Analysis performed on FAS participants within the EP. Here number analyzed signifies number of FAS participants with available data for each visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in rFVIIIFc Incremental Recovery (IR)</title>
          <description>Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (&lt;)0.5 IU/dL was set to 0 IU/dL for calculation of IR.</description>
          <population>Analysis performed on FAS participants within the EP. Here number analyzed signifies number of FAS participants with available data for each visit.</population>
          <units>IU/dL per IU/kg</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="101"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="35"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-1.26" upper_limit="-0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" lower_limit="-1.50" upper_limit="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" lower_limit="-1.06" upper_limit="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-1.09" upper_limit="-0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" lower_limit="-1.06" upper_limit="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 72</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" lower_limit="-1.10" upper_limit="-0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 84</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" lower_limit="-1.55" upper_limit="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 96</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" lower_limit="-1.21" upper_limit="-0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 108</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" lower_limit="-2.68" upper_limit="-0.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 120</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" lower_limit="-0.6" upper_limit="-0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Response to Immune Tolerance Induction (ITI)</title>
        <description>Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR &gt;=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life &gt;=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on ITI analysis set which was defined as all participants who consented to and initiated the ITI sub-study.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
            <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Response to Immune Tolerance Induction (ITI)</title>
          <description>Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR &gt;=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life &gt;=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.</description>
          <population>Analysis performed on ITI analysis set which was defined as all participants who consented to and initiated the ITI sub-study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Success</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Success</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Early Withdrawal</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ITI Ongoing at end of Study</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All Adverse Events (AEs) were collected from signature of the informed consent form up to end of the study (up to 3 years) regardless of seriousness or relationship to investigational product.</time_frame>
      <desc>Reported AEs are treatment-emergent AEs i.e. AE that was present prior to receiving first injection of rFVIIIFc and subsequently worsened in severity, or was not present prior to receiving first injection but subsequently appeared before last visit/follow-up call, whichever came later. Analysis performed on safety analysis set.</desc>
      <group_list>
        <group group_id="E1">
          <title>Recombinant Coagulation Factor VIII Fc Fusion Protein</title>
          <description>Participants were to receive rFVIIIFc as follows -PR: rFVIIIFc 25-80 IU/kg, at 3- to 5-day intervals until participant reached &gt;= 50 exposure days (ED: 24-hour period in which &gt;=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (&gt;=5.00 BU/mL) or positive low titer inhibitor (&gt;=0.60 and &lt;5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDra 22.0</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="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="60" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Factor viii inhibition</sub_title>
                <counts group_id="E1" events="29" subjects_affected="28" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Spontaneous haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Tongue haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Device related thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Gastroenteritis norovirus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Haematoma infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Meningitis aseptic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Parainfluenzae virus infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Rotavirus infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Staphylococcal skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Facial bones fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="19" subjects_affected="11" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="13" subjects_affected="8" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Palate injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Traumatic haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vascular access site haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Haematoma muscle</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Soft tissue haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile convulsion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Intraventricular haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device issue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Arteriovenous fistula operation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Central venous catheter removal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Central venous catheterisation</sub_title>
                <counts group_id="E1" events="30" subjects_affected="26" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Ventriculo-peritoneal shunt</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Subgaleal haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDra 22.0</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="85" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency anaemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="23" subjects_affected="18" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" events="23" subjects_affected="12" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="47" subjects_affected="31" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="28" subjects_affected="19" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Hand-foot-and-mouth disease</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="54" subjects_affected="31" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="41" subjects_affected="28" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="32" subjects_affected="17" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="27" subjects_affected="11" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="16" subjects_affected="9" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="146" subjects_affected="52" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="63" subjects_affected="28" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Lip injury</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Mouth injury</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" events="19" subjects_affected="7" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vaccination complication</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="20" subjects_affected="13" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="12" subjects_affected="10" subjects_at_risk="103"/>
              </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>The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Bioverativ, a Sanofi company</organization>
      <phone>800-633-1610 ext 6</phone>
      <email>Contact-US@sanofi.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/NCT02234323
org study id: 997HA306
secondary id: 2013-005512-10
nct id: NCT02234323
lead sponsor: 
collaborator: 
has dmc: Yes
The primary objective of the study was to evaluate the safety of rFVIIIFc (BIIB031) in
      previously untreated participants (PUPs) with severe hemophilia A. The secondary objectives
      were to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding
      episodes in PUPs, to evaluate rFVIIIFc consumption for the prevention and treatment of
      bleeding episodes in PUPs, and to describe experience with the use of rFVIIIFc for immune
      tolerance induction (ITI) in participants with inhibitors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
time frame: Up to 3 years
description: A positive/confirmed inhibitor result occurs when a participant has a value >=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected >=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached >=10 EDs and had >=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received >=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
measure: Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
time frame: Up to 3 years
description: ABR was annualized number of bleeding episodes during efficacy period (EP) per participant annualized to a 1-year interval of time. Bleeding episodes were classified as spontaneous if parent/caregiver/participant records bleeding event when there is no known contributing factor such as definite trauma or antecedent "strenuous" activity and as traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP divided by total number of days during EP)*365.25. EP was sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimens of study excluding surgical/rehabilitation periods and large injection intervals (greater than [>]28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
measure: Annualized Number of Spontaneous Joint Bleeding Episodes
time frame: Up to 3 years
description: Bleeding episodes were classified as spontaneous if parent/caregiver/participant records a bleeding event when there was no known contributing factor such as a definite trauma or antecedent "strenuous" activity. Annualized spontaneous joint bleeding episodes = (Total number of spontaneous joint bleeding episodes during EP divided by total number of days during EP)*365.25. EP reflects sum of all intervals of time during which participants were treated with rFVIIIFc per treatment regimen excluding major and minor surgical/rehabilitation periods and large injection intervals (> 28 days). Bleeding episodes were summarized by treatment regimen. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
measure: Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
time frame: Up to 3 years
description: Using e-diary, each participant's parent/caregiver rated treatment response to any bleeding episode at approximately 8-12 hours from time of injection and prior to additional doses of rFVIIIFc given for same bleeding episodes, using 4-point scale: 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hour after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approximately 8 hour after injection, but possibly requiring more than 1 injection after 24-48 hour for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hour after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approximately 8 hour after initial injection. Participants included in more than 1 treatment regimen if their regimen changed during study.
measure: Total Number of Exposure Days (EDs)
time frame: Up to 3 years
description: An ED was defined as a 24-hour period in which a participant received one or more doses of rFVIIIFc injections, with the time of the first injection of rFVIIIFc defined as the start of the ED. Participants who did not have a particular injection type were counted as having zero injections for that type.
measure: Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
time frame: Up to 3 years
description: Total annualized rFVIIIFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFVIIIFc during EP divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants are treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (>28 days). Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
measure: Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode
time frame: Up to 3 years
description: Number of Injections of rFVIIIFc required to resolve a bleeding episode during EP were reported. EP reflects the sum of all intervals of time during which participants were treated with rFVIIIFc according to the treatment regimens of the study excluding surgical/rehabilitation periods and large injection intervals (>28 days). All injections given from the initial sign of a bleed, until the last date/time within the bleed window were counted. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
measure: Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode
time frame: Up to 3 years
description: The average dose of rFVIIIFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during EP. EP begins with the first treatment regimen dose of rFVIIIFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods were not included in the EP. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.
measure: Change From Baseline in rFVIIIFc Incremental Recovery (IR)
time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
description: Blood samples were taken at trough (predose) and Cmax (maximum concentration) for assessment of incremental recovery, measured by the one-stage clotting assay. IR (International Units per deciliter [IU/dL] per IU/kg) = (Cmax for FVIII activity - Pre-dose FVIII activity) (IU/dL) divided by actual dose (IU/kg), where Cmax (maximum concentration) is 30-minute FVIII activity post-dose and FVIII activity less than (<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
measure: Number of Participants With Response to Immune Tolerance Induction (ITI)
time frame: Up to 3 years
description: Complete Success was defined as meeting all of the following criteria: Negative inhibitor titers in 2 consecutive determinations at least 4 weeks apart; IR >=66% of baseline in 2 consecutive determinations at least 4 weeks apart; Half life >=6 hours. Partial Success was defined as meeting the first criteria for complete success and one of the other 2 after 33 months of ITI.
arm group label: rFVIIIFc
arm group type: Experimental
description: Participants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (>=) 50 exposure days (ED: 24-hour period in which >=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (>=5.00 Bethesda Units per milliliter [BU/mL]) or positive low titer inhibitor (>=0.60 and <5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
intervention type: Biological
intervention name: rFVIIIFc
description: Administered as specified in arm description
arm group label: rFVIIIFc
other name: Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]
other name: Fc fusion protein
criteria: 
gender: Male
minimum age: N/A
maximum age: 5 Years
healthy volunteers: No
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country: Australia
country: Brazil
country: Canada
country: France
country: Germany
country: Ireland
country: Italy
country: Netherlands
country: New Zealand
country: Poland
country: Spain
country: Sweden
country: United Kingdom
country: United States
country: Denmark
responsible party type: Sponsor
mesh term: Hemophilia A
mesh term: Factor VIII
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
provided document: 
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certain agreements: 
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