Long-term Follow-up Study of Male Adults With Hemophilia B Previously Treated With Etranacogene Dezaparvovec (CSL222) (IX-TEND 3003)

An Extension Study Assessing the Long-term Safety and Efficacy of Etranacogene Dezaparvovec (CSL222) Previously Administered to Adult Male Subjects With Hemophilia B

The primary purpose of this study is to assess the long-term safety and efficacy in male adults with hemophilia B who were treated with CSL222 (CSL222) in parent studies CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).

Study Overview

• Status: Enrolling by invitation
• Conditions: Hemophilia B
• Intervention / Treatment: Genetic: AAV5-hFIXco-Padua

• Study Type: Observational
• Enrollment (Estimated): 56

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • 11-31 Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • 11-30 Universitair Ziekenhuis Leuven
• Denmark
  • Copenhagen, Denmark, 2100
    • 12-32 Rigshospitalet
• Germany
  • Berlin, Germany, 10249
    • 15-42 Vivantes Klinikum im Friedrichshain - Landsberger Allee
• Ireland
  • Dublin, Ireland, D08 A978
    • 19-56 St. James Hospital
• Netherlands
  • Amsterdam Zuidoost, Netherlands, 1105 AZ
    • 13-33 Amsterdam Universitair Medische Centra (UMC)
  • Groningen, Netherlands, 9713 GZ
    • 13-35 University Medical Center Groningen
  • Rotterdam, Netherlands
    • 13-34 Erasmus University Medical Center
  • Utrecht, Netherlands, 3584 CX
    • 13-36 Universitair Medisch Centrum Utrecht
• Sweden
  • Malmo, Sweden, SE-205 02
    • 16-43 Skane University Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • 18-54 Addenbrooke's Hospital
  • Southampton, United Kingdom, SO16 6YD
    • 18-53 University Hospital Southampton NHS Foundation Trust
  • England
    • London, England, United Kingdom, E1 1FR.
      • 18-52 Barts Health NHS Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • 10-15 Phoenix Childrens Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • 10-14 Arkansas Children's Hospital - Pharmacology
  • California
    • Los Angeles, California, United States, 90007
      • 10-22 Orthopaedic Institute for Children
    • Los Angeles, California, United States, 90027
      • 10-21 Children's Hospital of Los Angeles
    • Sacramento, California, United States, 95817
      • 10-63 UC Davis Medical Center
    • San Diego, California, United States, 92121
      • 10-12 University of California, San Diego (UCSD)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • 10-25 University of Colorado Denver
  • Florida
    • Tampa, Florida, United States, 33612
      • 10-19 University of South Florida
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • 10-10 University of Michigan Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • 10-16 University of North Carolina at Chapel Hill
  • Oregon
    • Portland, Oregon, United States, 97239
      • 10-18 Oregon Health & Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • 10-20 Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • 10-28 University of Texas Health Science Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • 10-26 University of Utah
  • Washington
    • Seattle, Washington, United States, 98104
      • 10-62 Washington Institute for Coagulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult male participants with hemophilia B who were previously treated with CSL222 in study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).

Description

Inclusion Criteria:

Received treatment with CSL222 in Study CSL222_2001 or Study CSL222_3001, and completed participation in Study CSL222_2001 or Study CSL222_3001 or at least 5 years have passed since receiving CSL222.

Exclusion Criteria:

Not Applicable

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CSL222; Participants who received CSL222 and completed either the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891) will be followed up from Year 5 after administration of CSL222 in parent study up to Year 15.	Genetic: AAV5-hFIXco-Padua; Single intravenous infusion of AAV5-hFIXco-Padua in the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).; Other Names: Etranacogene dezaparvovec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs)	From Year 5 after administration of CSL222 in parent study up to Year 15
Percentage of Participants With SAEs and AESIs	From Year 5 after administration of CSL222 in parent study up to Year 15
Number of SAEs and AESIs	From Year 5 after administration of CSL222 in parent study up to Year 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Bleeding Rate (ABR)	The total, spontaneous, joint, and traumatic bleeds will be analyzed.	From Year 5 after administration of CSL222 in parent study up to Year 15
Number of Participants With Zero Total, Spontaneous, Joint, and Traumatic Bleeding Episodes		From Year 5 after administration of CSL222 in parent study up to Year 15
Endogenous Factor IX (FIX) Activity	Endogenous FIX activity (expressed as percentage [%]) will be assessed using the one-stage activated partial thromboplastin time assay and a chromogenic assay.	From Year 5 after administration of CSL222 in parent study up to Year 15
Change from Baseline by Visit in Endogenous FIX Activity	Endogenous FIX activity (expressed as %) will be assessed using the one-stage activated partial thromboplastin time assay and a chromogenic assay.	At Baseline (in parent study), From Year 5 after administration of CSL222 in parent study up to Year 15
Annualized Consumption of FIX Replacement Therapy	The annualized consumption of FIX replacement therapy (excluding FIX replacement for invasive procedures) will be provided.	From Year 5 after administration of CSL222 in parent study up to Year 15
Annualized Infusion Rate of FIX Replacement Therapy	Annualized infusion rate of FIX replacement therapy (excluding FIX replacement for invasive procedures) will be provided.	From Year 5 after administration of CSL222 in parent study up to Year 15
Number of Participants Remaining Free of Continuous FIX Prophylaxis		From Year 5 after administration of CSL222 in parent study up to Year 15
Percentage of Participants Remaining Free of Continuous FIX Prophylaxis		From Year 5 after administration of CSL222 in parent study up to Year 15
Number of New Target Joints		From Year 5 after administration of CSL222 in parent study up to Year 15
Percentage Resolution of Pre-existing Target Joints		From Year 5 after administration of CSL222 in parent study up to Year 15
EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Index Value	The EQ-5D-5L questionnaire consists of the EQ-5D-5L descriptive system and the EQ-5D visual analogue scale (VAS). The EQ-5D-5L descriptive system of health-related quality of life (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 responses will be converted into a single overall health state utility value. This utility value will be derived using the EQ-5D-5L Crosswalk Index Value Calculator v2.xls [Hernández Alava et al, 2023], using the United Kingdom value set.	From Year 5 after administration of CSL222 in parent study up to Year 15
Change From Baseline in EQ-5D-5L Index Value	The EQ-5D-5L questionnaire consists of the EQ-5D-5L descriptive system and the EQ-5D 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 responses will be converted into a single overall health state utility value. This utility value will be derived using the EQ-5D-5L Crosswalk Index Value Calculator v2.xls [Hernández Alava et al, 2023], using the United Kingdom value set.	Baseline (in parent study), From Year 5 after administration of CSL222 in parent study up to Year 15
EQ-5D VAS Score	The EQ-5D VAS, which measures overall health status on a vertical VAS, ranges from 0 to 100. A higher score indicates better QoL.	From Year 5 after administration of CSL222 in parent study up to Year 15
Change From Baseline in EQ-5D VAS Score	The EQ-5D VAS, which measures overall health status on a vertical VAS, ranges from 0 to 100. A higher score indicates better QoL.	Baseline (in parent study), From Year 5 after administration of CSL222 in parent study up to Year 15
Hemophilia Quality of Life Questionnaire (Hem-A-QoL) Total Score	The Hem-A-QoL consists of 46 items comprising 10 domains: physical health, feelings, treatment, work and school, dealing with hemophilia, family planning, future, partnerships and sexuality, sports and leisure, and view of yourself for which responses will be recorded from 5 options (never, seldom, sometimes, often, and always; for some items, there is also a "not applicable" option). The total score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflecting a better QoL.	From Year 5 after administration of CSL222 in parent study up to Year 15
Change From Baseline in Hem-A-QoL Total Score	The Hem-A-QoL consists of 46 items comprising 10 domains: physical health, feelings, treatment, work and school, dealing with hemophilia, family planning, future, partnerships and sexuality, sports and leisure, and view of yourself for which responses will be recorded from 5 options (never, seldom, sometimes, often, and always; for some items, there is also a "not applicable" option). The total score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflecting a better QoL.	Baseline (in parent study), From Year 5 after administration of CSL222 in parent study up to Year 15

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2023
• Primary Completion (Estimated): March 23, 2035
• Study Completion (Estimated): March 23, 2035

Study Registration Dates

• First Submitted: July 18, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: CSL222_3003; EU CT Number (Other Identifier: 2023-503184-42)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

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 Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No