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/NCT05962398</url>
    </required_header>
    <id_info>
      <org_study_id>CSL222_3003</org_study_id>
      <nct_id>NCT05962398</nct_id>
    </id_info>
    <brief_title>Long-term Follow-up Study of Male Adults With Hemophilia B Previously Treated With Etranacogene Dezaparvovec (CSL222)</brief_title>
    <official_title>An Extension Study Assessing the Long-term Safety and Efficacy of Etranacogene Dezaparvovec (CSL222) Previously Administered to Adult Male Subjects 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>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary purpose of this study is to assess the long-term safety in male adults with&#xD;
        hemophilia B who were treated with CSL222 in studies CSL222_2001 (NCT03489291) or CSL222_3001&#xD;
        (NCT03569891).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">August 25, 2023</start_date>
    <completion_date type="Anticipated">March 2035</completion_date>
    <primary_completion_date type="Anticipated">March 2035</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>Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Percentage of Participants With SAEs and AESIs</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of SAEs and AESIs</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of Bleeding Episodes</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>The total, spontaneous, traumatic, and joint bleeds will be analyzed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Annualized Bleeding Rate (ABR)</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>The total, spontaneous, traumatic, and joint bleeds will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants With Zero Bleeds</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Correlation Analysis of ABR as a Function of Mean Factor IX (FIX) Activity</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>Correlation between ABR and mean FIX activity will be explored using a statistical modeling approach (like, generalized estimating equations [GEE] model for ABR with mean FIX activity as the independent variable).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants With FIX Activity</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>FIX activity will be assessed using the one-stage activated partial thromboplastin time assay and a chromogenic assay.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Using FIX Replacement Therapy</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Remaining Free of Previous Continuous Routine FIX Prophylaxis</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants With New Target Joints</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of Resolution of Target Joints</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score</measure>
      <time_frame>From Year 5.5 after administration of CSL222 in parent study up to Year 15</time_frame>
      <description>The EQ-5D-5L questionnaire consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (VAS). The EQ-5D-5L descriptive system of health-related QoL consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which responses will be recorded on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems). The EQ VAS overall score ranges from 0 to 100. A higher score indicates better QoL.</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Hemophilia B</condition>
    <arm_group>
      <arm_group_label>CSL222</arm_group_label>
      <description>Participants who received CSL222 and completed either the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891) will be followed up from Year 5.5 after administration of CSL222 in parent study up to Year 15.</description>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>AAV5-hFIXco-Padua</intervention_name>
      <description>Single intravenous infusion of AAV5-hFIXco-Padua in the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).</description>
      <arm_group_label>CSL222</arm_group_label>
      <other_name>Etranacogene dezaparvovec</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Adult male participants with hemophilia B who were previously treated with CSL222 in study&#xD;
          CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Treatment with CSL222 in Study CSL222_2001 or Study CSL222_3001.&#xD;
  &#xD;
            -  Provided written informed consent.&#xD;
  &#xD;
            -  Willing and able to adhere to all protocol requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          -&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Study Director</last_name>
      <role>Study Director</role>
      <affiliation>CSL Behring LLC</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>University of California, San Diego (UCSD)</name>
        <address>
          <city>San Diego</city>
          <state>California</state>
          <zip>92121</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>July 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <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/NCT05962398
  org study id: CSL222_3003
  nct id: NCT05962398
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary purpose of this study is to assess the long-term safety in male adults with
        hemophilia B who were treated with CSL222 in studies CSL222_2001 (NCT03489291) or CSL222_3001
        (NCT03569891).
  observational model: Cohort
  time perspective: Prospective
  measure: Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Percentage of Participants With SAEs and AESIs
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Number of SAEs and AESIs
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Number of Bleeding Episodes
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: The total, spontaneous, traumatic, and joint bleeds will be analyzed.
  measure: Annualized Bleeding Rate (ABR)
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: The total, spontaneous, traumatic, and joint bleeds will be analyzed. ABR is calculated as the total bleeding episodes divided by the total time at risk.
  measure: Number of Participants With Zero Bleeds
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Correlation Analysis of ABR as a Function of Mean Factor IX (FIX) Activity
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: Correlation between ABR and mean FIX activity will be explored using a statistical modeling approach (like, generalized estimating equations [GEE] model for ABR with mean FIX activity as the independent variable).
  measure: Number of Participants With FIX Activity
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: FIX activity will be assessed using the one-stage activated partial thromboplastin time assay and a chromogenic assay.
  measure: Number of Participants Using FIX Replacement Therapy
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Number of Participants Remaining Free of Previous Continuous Routine FIX Prophylaxis
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  measure: Number of Participants With New Target Joints
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period.
  measure: Percentage of Resolution of Target Joints
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period.
  measure: EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) VAS Overall Score
  time frame: From Year 5.5 after administration of CSL222 in parent study up to Year 15
  description: The EQ-5D-5L questionnaire consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (VAS). The EQ-5D-5L descriptive system of health-related QoL consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for which responses will be recorded on 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems). The EQ VAS overall score ranges from 0 to 100. A higher score indicates better QoL.
  arm group label: CSL222
  description: Participants who received CSL222 and completed either the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891) will be followed up from Year 5.5 after administration of CSL222 in parent study up to Year 15.
  intervention type: Genetic
  intervention name: AAV5-hFIXco-Padua
  description: Single intravenous infusion of AAV5-hFIXco-Padua in the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).
  arm group label: CSL222
  other name: Etranacogene dezaparvovec
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: Male
  gender based: Yes
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Study Director
  role: Study Director
  affiliation: CSL Behring LLC
  facility: 
  country: United States
  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.