<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/NCT02234310</url>
  </required_header>
  <id_info>
    <org_study_id>998HB303</org_study_id>
    <secondary_id>2013-003629-27</secondary_id>
    <nct_id>NCT02234310</nct_id>
  </id_info>
  <brief_title>Study to Determine the Safety and Efficacy of rFIXFc in Previously Untreated Males With Severe Hemophilia B</brief_title>
  <acronym>PUPs B-LONG</acronym>
  <official_title>An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc; BIIB029) in the Prevention and Treatment of Bleeding in Previously Untreated Patients With Severe Hemophilia B</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 recombinant coagulation&#xD;
      factor IX Fc fusion protein (rFIXFc, BIIB029) in previously untreated patients (PUPs) with&#xD;
      severe hemophilia B. Secondary objectives were to evaluate the efficacy of rFIXFc in the&#xD;
      prevention and treatment of bleeding episodes in PUPs, and to evaluate rFIXFc consumption for&#xD;
      prevention and treatment of bleeding episodes in PUPs.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 13, 2014</start_date>
  <completion_date type="Actual">August 20, 2019</completion_date>
  <primary_completion_date type="Actual">August 20, 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>Development of an inhibitor was defined as an inhibitor test result of &gt;= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of &gt;=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.</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 normalized 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 traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens 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 is 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 efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor 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 rFIXFc 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 (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. Participants were included in summary of 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 rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant 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 rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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 rFIXFc Required to Resolve a Bleeding Episode</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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 rFIXFc Required to Resolve a Bleeding Episode</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are 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 rFIXFc Incremental Recovery (IR)</measure>
    <time_frame>Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144</time_frame>
    <description>Blood samples were taken at trough 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 FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX activity less than (&lt;)0.5 IU/dL was set to 0 IU/dL for calculation of IR.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Hemophilia B</condition>
  <arm_group>
    <arm_group_label>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (&gt;=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX (FIX) levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rFIXFc</intervention_name>
    <description>Adjustments to the dose and interval of rFIXFc was made in this study based on investigator discretion using available pharmacokinetic (PK) data, subsequent FIX trough and peak levels, level of physical activity, and bleeding pattern, in accordance with local standards of care for a prophylactic regimen. There was an option to start study dosing as episodic treatment (on-demand).</description>
    <arm_group_label>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</arm_group_label>
    <other_name>BIIB029</other_name>
    <other_name>Alprolix</other_name>
    <other_name>recombinant coagulation factor IX Fc fusion protein</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Weight &gt;=3.5 kilogram at the time of informed consent.&#xD;
&#xD;
          -  Severe hemophilia B was defined as less than or equal to (&lt;=)2 International Units per&#xD;
             deciliter (IU/dL) (&lt;=2 percent [%]) endogenous FIX documented in the medical record or&#xD;
             as tested during the Screening Period.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  History of positive inhibitor testing. A prior history of inhibitors was defined based&#xD;
             on a participant's historical positive inhibitor test using the local laboratory&#xD;
             Bethesda value for a positive inhibitor test (that is equal to or above lower limit of&#xD;
             detection).&#xD;
&#xD;
          -  History of hypersensitivity reactions associated with any rFIXFc administration.&#xD;
&#xD;
          -  Exposure to blood components or injection with a coagulation factor IX (FIX)&#xD;
             concentrate (including plasma derived) other than rFIXFc.&#xD;
&#xD;
          -  Injection with commercially available rFIXFc more than 28 days prior to Screening.&#xD;
&#xD;
          -  More than 3 injections of commercially available rFIXFc prior to confirmation of&#xD;
             eligibility.&#xD;
&#xD;
          -  Other coagulation disorders in addition to hemophilia B.&#xD;
&#xD;
          -  Any concurrent clinically significant major disease that, in the opinion of the&#xD;
             Investigator, would have made the participant unsuitable for enrollment (example HIV&#xD;
             infection with cluster of differentiation 4 (CD4) lymphocyte count less than (&lt;)200&#xD;
             cells/microliter (mcL) or a viral load greater than (&gt;)200 particles/mcL, or any other&#xD;
             known congenital or acquired immunodeficiency).&#xD;
&#xD;
          -  Current systemic treatment with chemotherapy and/or other immunosuppressant drugs. Use&#xD;
             of steroids for treatment of asthma or management of acute allergic episodes or&#xD;
             otherwise life-threatening episodes was allowed. Treatment in these circumstances&#xD;
             should not have exceeded a 14-day duration.&#xD;
&#xD;
          -  Participation within the past 30 days in any other clinical study involving&#xD;
             investigational treatment.&#xD;
&#xD;
          -  Current enrollment in any other clinical study involving investigational treatment.&#xD;
&#xD;
          -  Inability to comply with study requirements.&#xD;
&#xD;
          -  Other unspecified reasons that, in the opinion of the Investigator or Bioverativ,&#xD;
             would have made the participant unsuitable for enrollment.&#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>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</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>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</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>Traverse City</city>
        <state>Michigan</state>
        <zip>49684</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>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aarhus</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Cardiologique - CHU Lille</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lyon Cedex 3</city>
        <state>Rhone</state>
        <zip>69437</zip>
        <country>France</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>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Napoli</city>
        <zip>80122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parma</city>
        <zip>43126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Roma</city>
        <zip>00165</zip>
        <country>Italy</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>Warszawa</city>
        <zip>02-091</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Malmo</city>
        <zip>205 02</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>Whitechapel</city>
        <state>London</state>
        <zip>E1 1BB</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_countries>
    <country>Australia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>New Zealand</country>
    <country>Poland</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </removed_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 17, 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 15, 2020</results_first_submitted>
  <results_first_submitted_qc>July 15, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 31, 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">March 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prophylaxis treatment</keyword>
  <keyword>episodic treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
    <mesh_term>Hemophilia B</mesh_term>
  </condition_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>August 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02234310/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 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02234310/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 28 active centers in 11 countries. Participants were screened between 13-Nov-2014 to 23-Jul-2018.</recruitment_details>
      <pre_assignment_details>A total of 38 participants were screened. A total of 33 participants were enrolled, 22 participants began study participation on episodic treatment regimen and 11 participants began study participation on prophylactic treatment regimen.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</title>
          <description>Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (&gt;=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Episodic Treatment Regimen</title>
              <participants_list>
                <participants group_id="P1" count="22">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="28">17 participants among the 22 who started in episodic regimen, switched to the prophylactic regimen.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Eligibility Criteria not fulfilled</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis was performed on Safety Analysis Set which included all participants who received at least 1 dose of study rFIXFc.</population>
      <group_list>
        <group group_id="B1">
          <title>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</title>
          <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="33"/>
          </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="0.60" lower_limit="0.08" upper_limit="2.00"/>
                  </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="33"/>
                  </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>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African-American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown or Not reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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>Development of an inhibitor was defined as an inhibitor test result of &gt;= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of &gt;=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.</description>
        <time_frame>Up to 3 years</time_frame>
        <population>Analysis performed on Safety Analysis set which included all participants who had received at least 1 dose of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay</title>
          <description>Development of an inhibitor was defined as an inhibitor test result of &gt;= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of &gt;=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.</description>
          <population>Analysis performed on Safety Analysis set which included all participants who had received at least 1 dose of study treatment.</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="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.03" lower_limit="0.08" upper_limit="15.76"/>
                  </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 normalized 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 traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens 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) which included all enrolled participants with at least 1 dose of study treatment. 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</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 normalized 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 traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens 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) which included all enrolled participants with at least 1 dose of study treatment. 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>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </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="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21" lower_limit="0.0" upper_limit="6.8"/>
                  </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="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.24" lower_limit="0.0" upper_limit="5.4"/>
                  </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 is 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 efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor 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. 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</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 is 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 efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor 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. 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>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </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="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="5.6"/>
                  </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="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of rFIXFc 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 (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. 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. Analysis was 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of rFIXFc 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 (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. Participants were included in summary of more than 1 treatment regimen if their regimen changed during study.</description>
          <population>Analysis performed on FAS. Analysis was 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="33"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>responses to injections</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="154"/>
              </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="33"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>responses to injections</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="80"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Excellent or Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Response not provided</title>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                  </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="33"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>responses to injections</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="74"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Excellent or Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Response not provided</title>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </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 rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</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 rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant 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="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.0" lower_limit="1" upper_limit="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</title>
        <description>Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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. 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes</title>
          <description>Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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. 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="33"/>
              </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="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="203.2" lower_limit="0" upper_limit="5719"/>
                  </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="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3175.0" lower_limit="2544" upper_limit="13164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Injections of rFIXFc Required to Resolve a Bleeding Episode</title>
        <description>Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Injections of rFIXFc Required to Resolve a Bleeding Episode</title>
          <description>Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.</population>
          <units>injections</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
              </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="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Bleeding episodes</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="31"/>
                  </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="28"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Bleeding episodes</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="1" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Average Dose Per Injection of rFIXFc Required to Resolve a Bleeding Episode</title>
        <description>The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are 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. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.</population>
        <group_list>
          <group group_id="O1">
            <title>Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Average Dose Per Injection of rFIXFc Required to Resolve a Bleeding Episode</title>
          <description>The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are 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. Here, number analyzed signifies number of bleeding episodes reported for each treatment regimen.</population>
          <units>IU/kg</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Bleeding episodes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Bleeding episodes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="85"/>
              </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="22"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Bleeding episodes</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.50" lower_limit="41.7" upper_limit="178.6"/>
                  </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="28"/>
                  </count_list>
                </analyzed>
                <analyzed>
                  <units>Bleeding episodes</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.92" lower_limit="23.3" upper_limit="181.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in rFIXFc Incremental Recovery (IR)</title>
        <description>Blood samples were taken at trough 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 FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX 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, 120, 132, and 144</time_frame>
        <population>Analysis performed on FAS. 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 IX Fc Fusion Protein (rFIXFc)</title>
            <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in rFIXFc Incremental Recovery (IR)</title>
          <description>Blood samples were taken at trough 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 FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX activity less than (&lt;)0.5 IU/dL was set to 0 IU/dL for calculation of IR.</description>
          <population>Analysis performed on FAS. 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="33"/>
              </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="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-0.08" upper_limit="0.12"/>
                  </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="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-0.17" upper_limit="0.15"/>
                  </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="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0" lower_limit="-0.18" upper_limit="0.11"/>
                  </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="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0" lower_limit="-0.13" upper_limit="0.03"/>
                  </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="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" lower_limit="-0.1" upper_limit="0.03"/>
                  </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="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" lower_limit="-0.20" upper_limit="0.07"/>
                  </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="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" lower_limit="-0.23" upper_limit="-0.04"/>
                  </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="-0.1" lower_limit="-0.14" upper_limit="0.03"/>
                  </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="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" lower_limit="-0.36" upper_limit="-0.01"/>
                  </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="-0.1" lower_limit="-0.1" upper_limit="-0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 132</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="-0.1" lower_limit="-0.1" upper_limit="-0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 144</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="0.0" lower_limit="0.0" upper_limit="0.0"/>
                  </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 AE are treatment-emergent AE i.e. AE that was present prior to receiving first injection of rFIXFc 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 IX Fc Fusion Protein (rFIXFc)</title>
          <description>Participants received rFIXFc IV injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 IU/kg weekly until a participant reached at least 50 exposure days (ED=24-hour period in which &gt;=1 injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.</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="0" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Factor ix inhibition</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Immune thrombocytopenic purpura</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Phimosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Tongue haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vessel puncture site haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Infusion site pustule</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Accidental exposure to product</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Face injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Skull fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Compartment syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Coma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Febrile convulsion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Spinal cord haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Tongue biting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prepuce redundant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Central venous catheterisation</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Poor venous access</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </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="27" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Middle ear effusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" events="15" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="33" subjects_affected="14" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Croup infectious</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Hand-foot-and-mouth disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="22" subjects_affected="11" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="33"/>
              </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="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="13" subjects_affected="7" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Balanoposthitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </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="3" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="11" subjects_affected="6" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="18" subjects_affected="6" subjects_at_risk="33"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis diaper</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Eczema</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="33"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="33"/>
              </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/NCT02234310
org study id: 998HB303
secondary id: 2013-003629-27
nct id: NCT02234310
lead sponsor: 
collaborator: 
has dmc: Yes
The primary objective of the study was to evaluate the safety of recombinant coagulation
      factor IX Fc fusion protein (rFIXFc, BIIB029) in previously untreated patients (PUPs) with
      severe hemophilia B. Secondary objectives were to evaluate the efficacy of rFIXFc in the
      prevention and treatment of bleeding episodes in PUPs, and to evaluate rFIXFc consumption for
      prevention and treatment of bleeding episodes in PUPs.
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: Development of an inhibitor was defined as an inhibitor test result of >= 0.60 Bethesda units per milliliter (BU/mL) that was confirmed by a second test result of >=0.60 BU/mL from a separate sample, drawn 2 to 4 weeks after the date when the original sample was drawn, with both tests performed by the central laboratory using Nijmegen-modified Bethesda assay.
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 normalized 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 traumatic when there is known reason for bleed. ABR=(Number of bleeding episodes during EP/total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimens 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 is 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 efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc per treatment regimen excluding major and minor 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 rFIXFc 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 (BE) at approximately 8 to 12 hours from time of injection and prior to additional doses of rFIXFc given for same BE using 4-point scale:- 1=Excellent: abrupt pain relief and/or improvement in signs of bleeding within approximately 8 hours after initial injection; 2=Good: definite pain relief and/or improvement in signs of bleeding within approx. 8 hours after injection, but possibly requiring more than 1 injection after 24-48 hours for complete resolution; 3=Moderate: Probable/slight beneficial effect within 8 hours after initial injection and requires more than 1 injection and 4=None: No improvement or condition worsens within approx. 8 hours after initial injection. Participants were included in summary of 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 rFIXFc injections, with the time of the first injection of rFIXFc defined as the start of the ED. Participant who did not have a particular injection type were counted as having zero injections for that type.
measure: Total Annualized rFIXFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
time frame: Up to 3 years
description: Total annualized rFIXFc consumption (in IU/kg) was calculated for each participant as: Annualized consumption = (Total IU/kg of rFIXFc during efficacy period (EP) divided by total number of days during EP)*365.25. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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 rFIXFc Required to Resolve a Bleeding Episode
time frame: Up to 3 years
description: Number of injections of rFIXFc required to resolve a bleeding episode during efficacy period (EP) were reported. EP reflects the sum of all intervals of time during which participants were treated with rFIXFc 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 rFIXFc Required to Resolve a Bleeding Episode
time frame: Up to 3 years
description: The average dose of rFIXFc per injection per bleeding episode was calculated as the average of all doses (IU/kg) administered to treat the bleeding episode during efficacy period (EP). EP begins with the first treatment regimen dose of rFIXFc and ends with the last dose (regardless of the reason for dosing). Surgery/rehabilitation periods are 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 rFIXFc Incremental Recovery (IR)
time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144
description: Blood samples were taken at trough 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 FIX activity - Pre-dose FIX activity) (IU/dL)/ Actual dose (IU/kg), where Cmax is 30 minute FIX activity post-dose and FIX activity less than (<)0.5 IU/dL was set to 0 IU/dL for calculation of IR.
arm group label: Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
arm group type: Experimental
description: Participants received rFIXFc intravenous (IV) injection as follows: Prophylactic treatment regimen: started with rFIXFc 50 International Units per kilogram (IU/kg) weekly until a participant reached at least 50 exposure days (ED=24-hour period in which greater than or equal to (>=1) injection/dose of rFIXFc was given) to rFIXFc, withdrawal from study or end of study. Adjustments to dose and dosing interval was based on incremental recovery, subsequent Factor IX (FIX) levels, physical activity, bleeding pattern, in accordance with local standards of care for prophylactic regimen (PR). Treatment with episodic (on demand) regimen can be initiated before PR at investigators discretion. Episodic (On demand; optional): rFIXFc at individual doses based on participant's clinical condition, type and severity of bleeding event until PR.
intervention type: Biological
intervention name: rFIXFc
description: Adjustments to the dose and interval of rFIXFc was made in this study based on investigator discretion using available pharmacokinetic (PK) data, subsequent FIX trough and peak levels, level of physical activity, and bleeding pattern, in accordance with local standards of care for a prophylactic regimen. There was an option to start study dosing as episodic treatment (on-demand).
arm group label: Recombinant Coagulation Factor IX Fc Fusion Protein (rFIXFc)
other name: BIIB029
other name: Alprolix
other name: recombinant coagulation factor IX Fc fusion protein
criteria: 
gender: Male
minimum age: N/A
maximum age: 17 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Denmark
country: France
country: Ireland
country: Italy
country: Netherlands
country: New Zealand
country: Poland
country: Sweden
country: United Kingdom
country: United States
country: Belgium
country: Canada
country: Germany
country: Spain
country: Switzerland
responsible party type: Sponsor
mesh term: Hemophilia A
mesh term: Hemophilia B
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: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 