xml: <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/NCT06008938</url>
    </required_header>
    <id_info>
      <org_study_id>CSL222_4001</org_study_id>
      <nct_id>NCT06008938</nct_id>
    </id_info>
    <brief_title>An Observational Cohort Study to Characterize the Effectiveness and Safety of HEMGENIX® in Patients With Hemophilia B</brief_title>
    <acronym>IX-TEND 4001</acronym>
    <official_title>An Observational Post-authorization Long-term Follow-up Study to Characterize the Effectiveness and Safety of HEMGENIX® (Etranacogene Dezaparvovec) in Patients With Hemophilia B</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>CSL Behring</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>CSL Behring</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
    </oversight_info>
    <brief_summary>
      <textblock>
        This observational, post-authorization, long-term follow-up study aims to investigate the&#xD;
        short and long-term effectiveness and safety of HEMGENIX in patients with hemophilia B. The&#xD;
        study will also include a cohort of patients with hemophilia B treated with FIX prophylaxis&#xD;
        to enable interpretation of relevant efficacy and safety findings of HEMGENIX.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">August 2043</completion_date>
    <primary_completion_date type="Anticipated">August 2043</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Bleeding Rate (all bleeds) - HEMGENIX Cohort</measure>
      <time_frame>During the 52 weeks following stable FIX expression (6 to 18 months) in the follow-up period and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.</time_frame>
      <description>Annualised Bleeding Rate (ABR) for all bleeds</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Bleeding Rate (specified bleed types) - HEMGENIX Cohort</measure>
      <time_frame>During follow-up period (52 weeks following stable FIX expression [6 to 18 months]), and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.</time_frame>
      <description>ABR for spontaneous, FIX-treated, traumatic, and joint bleeds</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Zero bleeds - HEMGENIX Cohort</measure>
      <time_frame>During follow-up after HEMGENIX treatment, up to 180 months</time_frame>
      <description>Number of patients with zero bleeds</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation analysis - HEMGENIX Cohort</measure>
      <time_frame>Over the 6 to: 18, 24, 36, 48, 60, 72, 96, 108, 120, 132, 144, 156, 168, and 180 months after HEMGENIX treatment.</time_frame>
      <description>Correlation analysis of ABR as a function of mean FIX activity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Bleeding Rate - FIX Prophylaxis Cohort</measure>
      <time_frame>In the period Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 Months.</time_frame>
      <description>ABR (total, spontaneous, FIX-treated, traumatic, and joint bleeds)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>FIX activity - HEMGENIX Cohort</measure>
      <time_frame>Day 1, Week 6, and Months 6, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.</time_frame>
      <description>Mean uncontaminated endogenous FIX activity (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized consumption of FIX replacement therapy - HEMGENIX Cohort</measure>
      <time_frame>During the follow-up periods (52 weeks following stable FIX expression [6 to 18 months], &amp; at Months 0 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180), &amp; at yearly intervals (ie, at 0 to 1 yr, 1 to 2 yrs, etc, up to 14 to 15 yrs).</time_frame>
      <description>Mean annualized consumption (IU/kg/Yr) of FIX replacement therapy (including FIX replacement for various clinical scenarios eg, prophylaxis, spontaneous bleeding events, medical procedures, surgery, and trauma).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized consumption of FIX replacement therapy - FIX Prophylaxis Cohort</measure>
      <time_frame>At Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180.</time_frame>
      <description>Mean annualized consumption (IU/kg/Yr) of FIX replacement therapy (including FIX replacement for various clinical scenarios eg, prophylaxis, spontaneous bleeding events, medical procedures, surgery, and trauma).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients remaining free of previous continuous routine prophylaxis - HEMGENIX Cohort</measure>
      <time_frame>At Months 6 to: 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.</time_frame>
      <description>Number and proportion of patients remaining free of previous continuous routine prophylaxis (FIX replacement therapy)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Target joints occurrence - HEMGENIX Cohort</measure>
      <time_frame>After HEMGENIX treatment, during the follow-up periods (52 weeks following stable FIX expression [6 to 18 months], and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180).</time_frame>
      <description>The annualized occurrence of target joints (defined as 3 or more spontaneous bleeding events into a single joint within a consecutive 6-month period).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Target joints resolution - HEMGENIX Cohort</measure>
      <time_frame>During the follow-up period, up to 180 months</time_frame>
      <description>The percentage of resolution of target joints (target resolution is defined as a recorded target joint with 2 or fewer spontaneous bleeding events within a consecutive 12-month period).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Target joints - FIX Prophylaxis Cohort</measure>
      <time_frame>From Months 0 to 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180.</time_frame>
      <description>The annualized occurrence of target joints</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Related Serious Adverse Events (SAEs) - number</measure>
      <time_frame>During 15 years of follow-up</time_frame>
      <description>Incidence (number) of related SAEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Related SAEs - percent</measure>
      <time_frame>During 15 years of follow-up</time_frame>
      <description>Incidence (percent) of related SAEs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events of Special Interest (AESIs) - number</measure>
      <time_frame>During 15 years of follow-up</time_frame>
      <description>Incidence (number) of AESIs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AESIs - percent</measure>
      <time_frame>During 15 years of follow-up</time_frame>
      <description>Incidence (percent) of AESIs</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">500</enrollment>
    <condition>Hemophilia B</condition>
    <arm_group>
      <arm_group_label>HEMGENIX</arm_group_label>
      <description>Patients with hemophilia B treated with HEMGENIX in countries where HEMGENIX is approved for commercial use.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>FIX Prophylaxis</arm_group_label>
      <description>Patients with hemophilia B on FIX prophylaxis and enrolled in American Thrombosis and Hemostasis Network (ATHN) Transcends (A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People with Non-Neoplastic Hematologic Disorders) Hemophilia Cohort, or a similar registry.</description>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>HEMGENIX</intervention_name>
      <description>HEMGENIX is a gene therapy medicinal product that aims to deliver a factor IX (FIX) gene expression cassette to the liver of patients with hemophilia B.</description>
      <arm_group_label>HEMGENIX</arm_group_label>
      <other_name>Etranacogene dezaparvovec</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Factor IX (FIX)</intervention_name>
      <description>FIX prophylaxis therapy</description>
      <arm_group_label>FIX Prophylaxis</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with hemophilia B who have been treated with HEMGENIX and are enrolled in either&#xD;
          the sponsor's study or the ATHN Transcends study (Hemophilia Cohort, Gene Therapy Outcomes&#xD;
          Arm), and patients who receive routine prophylaxis treatment with FIX replacement therapy&#xD;
          that are enrolled in the ATHN Transcends study (Hemophilia Cohort, Natural History Arm), or&#xD;
          a similar registry. All patients will provide signed informed consent required for&#xD;
          participation.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          HEMGENIX Cohort:&#xD;
  &#xD;
            -  Treatment with commercial HEMGENIX.&#xD;
  &#xD;
            -  Have provided signed written informed consent within 3 months before or within 6&#xD;
               months after HEMGENIX treatment, or within 6 months of when the study is initiated at&#xD;
               the participating site.&#xD;
  &#xD;
          FIX Prophylaxis Cohort:&#xD;
  &#xD;
            -  Adult patients (≥ 18 years) with hemophilia B who have consented and enrolled in ATHN&#xD;
               Transcends Hemophilia Cohort (or a similar registry) and are receiving FIX prophylaxis&#xD;
               therapy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          HEMGENIX Cohort:&#xD;
  &#xD;
            -  The patient population that will be observed in this study must not have been treated&#xD;
               with etranacogene dezaparvovec in a clinical trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Global Program Director</last_name>
      <role>Study Director</role>
      <affiliation>CSL Behring</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Trial Registration Coordinator</last_name>
      <phone>1-610-878-4000</phone>
      <email>clinicaltrials@cslbehring.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 23, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Hemophilia B</keyword>
    <keyword>HEMGENIX</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>CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.&#xD;
  Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.&#xD;
  If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.</ipd_time_frame>
      <ipd_access_criteria>Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.&#xD;
  An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.&#xD;
  The requesting party must execute an appropriate data sharing agreement before IPD will be made available.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06008938
  org study id: CSL222_4001
  nct id: NCT06008938
  lead sponsor: 
  has dmc: No
  This observational, post-authorization, long-term follow-up study aims to investigate the
        short and long-term effectiveness and safety of HEMGENIX in patients with hemophilia B. The
        study will also include a cohort of patients with hemophilia B treated with FIX prophylaxis
        to enable interpretation of relevant efficacy and safety findings of HEMGENIX.
  observational model: Cohort
  time perspective: Prospective
  measure: Bleeding Rate (all bleeds) - HEMGENIX Cohort
  time frame: During the 52 weeks following stable FIX expression (6 to 18 months) in the follow-up period and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.
  description: Annualised Bleeding Rate (ABR) for all bleeds
  measure: Bleeding Rate (specified bleed types) - HEMGENIX Cohort
  time frame: During follow-up period (52 weeks following stable FIX expression [6 to 18 months]), and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.
  description: ABR for spontaneous, FIX-treated, traumatic, and joint bleeds
  measure: Zero bleeds - HEMGENIX Cohort
  time frame: During follow-up after HEMGENIX treatment, up to 180 months
  description: Number of patients with zero bleeds
  measure: Correlation analysis - HEMGENIX Cohort
  time frame: Over the 6 to: 18, 24, 36, 48, 60, 72, 96, 108, 120, 132, 144, 156, 168, and 180 months after HEMGENIX treatment.
  description: Correlation analysis of ABR as a function of mean FIX activity.
  measure: Bleeding Rate - FIX Prophylaxis Cohort
  time frame: In the period Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 Months.
  description: ABR (total, spontaneous, FIX-treated, traumatic, and joint bleeds)
  measure: FIX activity - HEMGENIX Cohort
  time frame: Day 1, Week 6, and Months 6, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.
  description: Mean uncontaminated endogenous FIX activity (%)
  measure: Annualized consumption of FIX replacement therapy - HEMGENIX Cohort
  time frame: During the follow-up periods (52 weeks following stable FIX expression [6 to 18 months], & at Months 0 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180), & at yearly intervals (ie, at 0 to 1 yr, 1 to 2 yrs, etc, up to 14 to 15 yrs).
  description: Mean annualized consumption (IU/kg/Yr) of FIX replacement therapy (including FIX replacement for various clinical scenarios eg, prophylaxis, spontaneous bleeding events, medical procedures, surgery, and trauma).
  measure: Annualized consumption of FIX replacement therapy - FIX Prophylaxis Cohort
  time frame: At Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180.
  description: Mean annualized consumption (IU/kg/Yr) of FIX replacement therapy (including FIX replacement for various clinical scenarios eg, prophylaxis, spontaneous bleeding events, medical procedures, surgery, and trauma).
  measure: Number of patients remaining free of previous continuous routine prophylaxis - HEMGENIX Cohort
  time frame: At Months 6 to: 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment.
  description: Number and proportion of patients remaining free of previous continuous routine prophylaxis (FIX replacement therapy)
  measure: Target joints occurrence - HEMGENIX Cohort
  time frame: After HEMGENIX treatment, during the follow-up periods (52 weeks following stable FIX expression [6 to 18 months], and at Months 6 to: 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180).
  description: The annualized occurrence of target joints (defined as 3 or more spontaneous bleeding events into a single joint within a consecutive 6-month period).
  measure: Target joints resolution - HEMGENIX Cohort
  time frame: During the follow-up period, up to 180 months
  description: The percentage of resolution of target joints (target resolution is defined as a recorded target joint with 2 or fewer spontaneous bleeding events within a consecutive 12-month period).
  measure: Target joints - FIX Prophylaxis Cohort
  time frame: From Months 0 to 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180.
  description: The annualized occurrence of target joints
  measure: Related Serious Adverse Events (SAEs) - number
  time frame: During 15 years of follow-up
  description: Incidence (number) of related SAEs
  measure: Related SAEs - percent
  time frame: During 15 years of follow-up
  description: Incidence (percent) of related SAEs
  measure: Adverse Events of Special Interest (AESIs) - number
  time frame: During 15 years of follow-up
  description: Incidence (number) of AESIs
  measure: AESIs - percent
  time frame: During 15 years of follow-up
  description: Incidence (percent) of AESIs
  arm group label: HEMGENIX
  description: Patients with hemophilia B treated with HEMGENIX in countries where HEMGENIX is approved for commercial use.
  arm group label: FIX Prophylaxis
  description: Patients with hemophilia B on FIX prophylaxis and enrolled in American Thrombosis and Hemostasis Network (ATHN) Transcends (A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People with Non-Neoplastic Hematologic Disorders) Hemophilia Cohort, or a similar registry.
  intervention type: Genetic
  intervention name: HEMGENIX
  description: HEMGENIX is a gene therapy medicinal product that aims to deliver a factor IX (FIX) gene expression cassette to the liver of patients with hemophilia B.
  arm group label: HEMGENIX
  other name: Etranacogene dezaparvovec
  intervention type: Biological
  intervention name: Factor IX (FIX)
  description: FIX prophylaxis therapy
  arm group label: FIX Prophylaxis
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Global Program Director
  role: Study Director
  affiliation: CSL Behring
  last name: Trial Registration Coordinator
  phone: 1-610-878-4000
  email: clinicaltrials@cslbehring.com
  responsible party type: Sponsor
  mesh term: Hemophilia A
  mesh term: Hemophilia B
  sharing ipd: Yes
  ipd description: CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
  Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.
  If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
  ipd access criteria: Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.
  An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.
  The requesting party must execute an appropriate data sharing agreement before IPD will be made available.