<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/NCT01712438</url>
  </required_header>
  <id_info>
    <org_study_id>GENA-05</org_study_id>
    <secondary_id>2012-002554-23</secondary_id>
    <nct_id>NCT01712438</nct_id>
  </id_info>
  <brief_title>Human Cell Line-derived Recombinant Factor VIII (Human-cl-rhFVIII) in Previously Untreated Patients</brief_title>
  <official_title>Immunogenicity, Efficacy and Safety of Treatment With Human-cl-rhFVIII in Previously Untreated Patients With Severe Hemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Octapharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Octapharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigate the inhibitor development rate of Human cl rhFVIII in previously untreated&#xD;
      patients with severe Hemophilia A.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">December 14, 2018</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>Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors</measure>
    <time_frame>maximum 5 years (100 exposure days)</time_frame>
    <description>The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to &lt;5 BU/mL for a &quot;low titre&quot; inhibitor and ≥5 BU/mL for a &quot;high-titre&quot; inhibitor.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Spontaneous Break-through Bleeds</measure>
    <time_frame>Maximum 5 years (100 exposure days)</time_frame>
    <description>The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of Human-cl rhFVIII for the Treatment of Bleeds</measure>
    <time_frame>Maximum 5 years (100 exposure days)</time_frame>
    <description>A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of Human-cl rhFVIII for Surgical Prophylaxis</measure>
    <time_frame>Maximum 5 years (100 exposure days)</time_frame>
    <description>An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>The Occurrence of Any Adverse Event (AE)</measure>
    <time_frame>5 years</time_frame>
    <description>The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Severe Hemophilia A</condition>
  <arm_group>
    <arm_group_label>Human cl rhFVIII</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human cl rhFVIII</intervention_name>
    <arm_group_label>Human cl rhFVIII</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patients&#xD;
&#xD;
          -  Severe Hemophilia A (FVIII:C &lt;1%)&#xD;
&#xD;
          -  No previous treatment with FVIII concentrates or other blood products containing FVIII&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis with a coagulation disorder other than Hemophilia A&#xD;
&#xD;
          -  Severe liver or kidney disease&#xD;
&#xD;
          -  Concomitant treatment with any systemic immunosuppressive drug&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sigurd Knaub</last_name>
    <role>Study Director</role>
    <affiliation>Octapharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UC Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All Children's Hospital</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harvard Children's Hospital Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Scientific Practical Center for Pediatric Oncology and Hematology</name>
      <address>
        <city>Minsk</city>
        <country>Belarus</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G2V2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BC Children's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V6H 3V4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mc Master Children's Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S4K1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Ste-Justine</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>L'hôpital Côte de Nacre - CHU de Caen</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de traitement de l'hemophilie, Hôpital Bicêtre</name>
      <address>
        <city>Le Kremlin-Bicêtre</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de la Timone</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôtel-Dieu de Nantes, Centre Regional de Traitement de l'hemophilie</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes - Hôpital Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Trousseau - CHU Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Haematology and Transfusiology</name>
      <address>
        <city>Tbilisi</city>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut für Experimentelle Hämatologie und Transfusionsmedizin (IHT)</name>
      <address>
        <city>Bonn</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Frankfurt/M</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin der Johannes-Gutenberg-Universität Mainz</name>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kasturba Medical College, Dr. TMA Pai Hospital</name>
      <address>
        <city>Manipala</city>
        <state>Karnataka</state>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahyadri Speciality Hospital, Haematology &amp; BMT Unit</name>
      <address>
        <city>Pune</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christian Medical College &amp; Hospital, Dept of Haematology</name>
      <address>
        <city>Vellore</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ. Di Perugia</name>
      <address>
        <city>Perugia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro di Referimento per le Malattie Emorragiche e Trombotiche</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific Research Institute of Mother and Child Health Care</name>
      <address>
        <city>Chisinau</city>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Ibn Sina</name>
      <address>
        <city>Rabat</city>
        <country>Morocco</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical School Warsaw</name>
      <address>
        <city>Warsaw</city>
        <zip>00-576</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HSJ - Hospital de São João, EPE</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morozovsky Children's Hospital</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haemophilia Centre, University Clinical Centre</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unitat d'hemofilia, Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Children's Specialized Hospital &quot;OHMATDET&quot;</name>
      <address>
        <city>Kiev</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Blood Pathology and Transfusion Medicine</name>
      <address>
        <city>Lviv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospital</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Ormond Street Hospital for Children</name>
      <address>
        <city>London</city>
        <zip>WC1N3JH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belarus</country>
    <country>Canada</country>
    <country>France</country>
    <country>Georgia</country>
    <country>Germany</country>
    <country>India</country>
    <country>Italy</country>
    <country>Moldova, Republic of</country>
    <country>Morocco</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Slovenia</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <results_first_submitted>September 25, 2019</results_first_submitted>
  <results_first_submitted_qc>October 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 21, 2019</results_first_posted>
  <last_update_submitted>December 21, 2020</last_update_submitted>
  <last_update_submitted_qc>December 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Previously untreated patients</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT01712438/Prot_002.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>April 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT01712438/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Human-cl rhFVIII</title>
          <description>Of the total number of patients that started in the study, the safety (SAF) and intent-to-treat (ITT) population received at least one treatment with Human-cl rhFVIII.&#xD;
Prophylactic treatment dose given to all patients in the PROPH population (all patients who received at least one administration of Human cI rhFVIII with prophylaxis documented as the reason for treatment): 20-50 IU/FVIII/kg body weight (BW)).&#xD;
On-demand treatment of bleeding episodes (BEs) dose given to the BLEED population (all patients with bleeding episodes treated with Human cI rhFVIII): 20-30 IU FVIII/kg BW (minor haemorrhage), 30-40 IU FVIII/kg BW (moderate to major haemorrhage) or 40-60 IU FVIII/kg BW (major to life-threatening haemorrhage). Surgical prophylaxis dose given to the SURG population (all patients with surgeries performed under Human cI rhFVIII treatment): 25-30 IU FVIII/kg BW (minor surgeries) or 40-60 IU FVIII/kg BW (major surgeries).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="110"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>SAF Population</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>ITT Population</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>PP Population</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>PROPH Population</title>
              <participants_list>
                <participants group_id="P1" count="103"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BLEED Population</title>
              <participants_list>
                <participants group_id="P1" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>SURG Population</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not treated with Human-cl rhFVIII</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing ITI treatment</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Violated inclusion &amp; exclusion criteria</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Prematurely Discontinued</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety (SAF) and intent-to-treat (ITT) population consist of all patients who had data collected post-treatment with Human-cl rhFVIII (n=108).</population>
      <group_list>
        <group group_id="B1">
          <title>Human-cl rhFVIII</title>
          <description>The safety (SAF) and intent-to-treat (ITT) population consists all patients who had data collected post-treatment with Human-cl rhFVIII (n=108).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="108"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age at screening in months</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.0" lower_limit="0" upper_limit="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <description>Age at exposure day 1 in months</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.6" lower_limit="0" upper_limit="146"/>
                  </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="108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="105"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI) at Exposure Day 1 (ED1)</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.2" lower_limit="9" upper_limit="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height at Exposure Day 1 (ED1)</title>
          <description>Height at exposure day 1 in centimeters</description>
          <units>centimeters (cm)</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.0" lower_limit="45" upper_limit="144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight at Exposure Day 1 (ED1)</title>
          <description>Weight at exposure day 1 in kilograms</description>
          <units>kilograms (kg)</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11.7" lower_limit="3" upper_limit="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Family history of inhibitors</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors</title>
        <description>The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to &lt;5 BU/mL for a &quot;low titre&quot; inhibitor and ≥5 BU/mL for a &quot;high-titre&quot; inhibitor.</description>
        <time_frame>maximum 5 years (100 exposure days)</time_frame>
        <population>The analysis was performed for the SAF/ITT population which includes all patients who had data collected post-treatment with Human-cl rhFVIII (n=108). Of the 108 patients, 105 patients had at least one inhibitor test after exposure day (ED) 1.</population>
        <group_list>
          <group group_id="O1">
            <title>SAF/ITT Population</title>
            <description>All patients who had data collected post-treatment with Human-cl rhFVIII (n=108).</description>
          </group>
        </group_list>
        <measure>
          <title>Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors</title>
          <description>The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to &lt;5 BU/mL for a &quot;low titre&quot; inhibitor and ≥5 BU/mL for a &quot;high-titre&quot; inhibitor.</description>
          <population>The analysis was performed for the SAF/ITT population which includes all patients who had data collected post-treatment with Human-cl rhFVIII (n=108). Of the 108 patients, 105 patients had at least one inhibitor test after exposure day (ED) 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>High titre inhibitor (&gt;5 BU/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Low titre inhibitor (&lt;5 BU/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any inhibitor (&gt;0.6 BU/mL)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Frequency of Spontaneous Break-through Bleeds</title>
        <description>The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII</description>
        <time_frame>Maximum 5 years (100 exposure days)</time_frame>
        <population>The analysis population includes all patients who received at least one prophylactic treatment with Human-cl rhFVIII (PROPH population; n=103). Of all patients in the PROPH population, data was available on spontaneous break-through bleeds for 102 patients.</population>
        <group_list>
          <group group_id="O1">
            <title>PROPH Population</title>
            <description>All patients who received at least one prophylactic treatment with Human-cl rhFVIII (n=103).</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Spontaneous Break-through Bleeds</title>
          <description>The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII</description>
          <population>The analysis population includes all patients who received at least one prophylactic treatment with Human-cl rhFVIII (PROPH population; n=103). Of all patients in the PROPH population, data was available on spontaneous break-through bleeds for 102 patients.</population>
          <units>No. BEs per duration (year) (ABR)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.976" lower_limit="0.431" upper_limit="1.521"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of Human-cl rhFVIII for the Treatment of Bleeds</title>
        <description>A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none).</description>
        <time_frame>Maximum 5 years (100 exposure days)</time_frame>
        <population>The analysis population includes patients (n=94) who received Human-cl rhFVIII for on-demand treatment of BEs (BLEED population).</population>
        <group_list>
          <group group_id="O1">
            <title>BLEED Population</title>
            <description>All patients that experienced at least one bleeding episode that was treated with Human-cl rhFVIII (n=94).</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Human-cl rhFVIII for the Treatment of Bleeds</title>
          <description>A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none).</description>
          <population>The analysis population includes patients (n=94) who received Human-cl rhFVIII for on-demand treatment of BEs (BLEED population).</population>
          <units>Number of Bleeding Events</units>
          <param>Count of Units</param>
          <units_analyzed>Number of Bleeding Events</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="94"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Number of Bleeding Events</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="804"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Excellent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Good</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="237"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>None</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy of Human-cl rhFVIII for Surgical Prophylaxis</title>
        <description>An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none).</description>
        <time_frame>Maximum 5 years (100 exposure days)</time_frame>
        <population>The analysis population includes 24 patients that received Human-cl rhFVIII for surgical prophylaxis during a total of 26 surgeries (SURG population). Of these, 13 patients had minor surgeries and 11 patients had major surgeries. Of the total 26 surgeries, 21 had an overall efficacy assessment (an assessment was not performed for 5 surgeries).</population>
        <group_list>
          <group group_id="O1">
            <title>Minor Surgeries</title>
            <description>All patients that had minor surgeries performed under Human-cl rhFVIII treatment (n=13)</description>
          </group>
          <group group_id="O2">
            <title>Major Surgeries</title>
            <description>All patients that had major surgeries performed under Human-cl rhFVIII treatment (n=11)</description>
          </group>
          <group group_id="O3">
            <title>All Surgeries</title>
            <description>All patients that had surgeries performed under Human-cl rhFVIII treatment (n=24)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of Human-cl rhFVIII for Surgical Prophylaxis</title>
          <description>An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none).</description>
          <population>The analysis population includes 24 patients that received Human-cl rhFVIII for surgical prophylaxis during a total of 26 surgeries (SURG population). Of these, 13 patients had minor surgeries and 11 patients had major surgeries. Of the total 26 surgeries, 21 had an overall efficacy assessment (an assessment was not performed for 5 surgeries).</population>
          <units>Number of surgeries</units>
          <param>Count of Units</param>
          <units_analyzed>Number of surgeries</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="24"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Number of surgeries</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Excellent</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Good</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Moderate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Occurrence of Any Adverse Event (AE)</title>
        <description>The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.</description>
        <time_frame>5 years</time_frame>
        <population>Of the 110 patients enrolled in the study, 2 were excluded because they had no treatment with Human-cl rhFVIII leaving 108 patients in the safety (SAF) and intent-to-treat (ITT) population.</population>
        <group_list>
          <group group_id="O1">
            <title>SAF/ITT Population</title>
            <description>All patients who had data collected post-treatment with Human-cl rhFVIII (n=108).</description>
          </group>
        </group_list>
        <measure>
          <title>The Occurrence of Any Adverse Event (AE)</title>
          <description>The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.</description>
          <population>Of the 110 patients enrolled in the study, 2 were excluded because they had no treatment with Human-cl rhFVIII leaving 108 patients in the safety (SAF) and intent-to-treat (ITT) population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="108"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Event (AE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse event (SAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temporally related adverse event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death due to probably/possibly related AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to permanent study discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Maximum 5 years (100 exposure days)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SAF/ITT Population</title>
          <description>All patients who had data collected post-treatment with Human-cl rhFVIII (n=108).</description>
        </group>
      </group_list>
      <serious_events>
        <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="108"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Factor VIII inhibition</sub_title>
                <counts group_id="E1" events="29" subjects_affected="28" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Factor IX inhibition</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Haemorrhagic anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Mouth haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Skin injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Traumatic haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Limb injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Scrotal haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Subdural haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Type 1 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Device Issue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Apnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <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="101" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Factor VIII inhibition</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Haemorrhagic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Teething</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="61" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Varicella</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Device related information</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Erythema infectiosum</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Head injury</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Mouth injury</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Rhinorrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="108"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="108"/>
              </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>Octapharma agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Octapharma supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. Octapharma also reserves the right to review data prior to publishing and provide comments/changes within a certain time period.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sylvia Werner</name_or_title>
      <organization>Octapharma</organization>
      <phone>415 260-9577</phone>
      <email>sylvia.werner@octapharma.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/NCT01712438
org study id: GENA-05
secondary id: 2012-002554-23
nct id: NCT01712438
lead sponsor: 
has dmc: Yes
Investigate the inhibitor development rate of Human cl rhFVIII in previously untreated
      patients with severe Hemophilia A.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Immunogenicity of Human-cl rhFVIII: Incidence of Inhibitors
time frame: maximum 5 years (100 exposure days)
description: The number of patients developing FVIII inhibitors was observed during the observation period by assessing inhibitor development using the modified Bethesda assay (Nijmegen modification). The definitions for thresholds were ≥0.6 to <5 BU/mL for a "low titre" inhibitor and ≥5 BU/mL for a "high-titre" inhibitor.
measure: Frequency of Spontaneous Break-through Bleeds
time frame: Maximum 5 years (100 exposure days)
description: The annualized bleeding rate (ABR) was calculated during inhibitor-free periods for spontaneous bleeding events (BEs) during prophylactic treatment with Human cl rhFVIII
measure: Efficacy of Human-cl rhFVIII for the Treatment of Bleeds
time frame: Maximum 5 years (100 exposure days)
description: A personal efficacy assessment to assess the efficacy of Human-cl rhFVIII for the on-demand treatment of bleeding episodes. Efficacy was assessed using a four-point scale (excellent, good, moderate, none).
measure: Efficacy of Human-cl rhFVIII for Surgical Prophylaxis
time frame: Maximum 5 years (100 exposure days)
description: An overall efficacy assessment to assess the efficacy of human-cl rhFVIII in surgical prophylaxis of minor and major surgeries. The efficacy assessment was analyzed using a four-point scale (excellent, good, moderate, none).
measure: The Occurrence of Any Adverse Event (AE)
time frame: 5 years
description: The frequency of AEs, as monitored throughout the whole study by the number of patients with at least one adverse event occurrence.
arm group label: Human cl rhFVIII
arm group type: Experimental
intervention type: Biological
intervention name: Human cl rhFVIII
arm group label: Human cl rhFVIII
criteria: 
gender: Male
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Sigurd Knaub
role: Study Director
affiliation: Octapharma
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country: Belarus
country: Canada
country: France
country: Georgia
country: Germany
country: India
country: Italy
country: Moldova, Republic of
country: Morocco
country: Poland
country: Portugal
country: Russian Federation
country: Slovenia
country: Spain
country: Ukraine
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Hemophilia A
provided document: 
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certain agreements: 
point of contact: 