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

Study Overview
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Brief Summary
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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).

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

Conditions
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Hemophilia B

Intervention / Treatment
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* Genetic: AAV5-hFIXco-Padua


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment with CSL222 in Study CSL222_2001 or Study CSL222_3001. Provided written informed consent. Willing and able to adhere to all protocol requirements. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CSL222<br>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<br>* Single intravenous infusion of AAV5-hFIXco-Padua in the study CSL222_2001 (NCT03489291) or CSL222_3001 (NCT03569891).<br>* Other names: Etranacogene dezaparvovec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |
| --- | --- | --- |
| Number of Bleeding Episodes | The total, spontaneous, traumatic, and joint bleeds will be analyzed. | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Annualized Bleeding Rate (ABR) | 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. | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Number of Participants With Zero Bleeds |  | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Correlation Analysis of ABR as a Function of Mean Factor IX (FIX) Activity | 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). | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Number of Participants With FIX Activity | FIX activity 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 | 
| Number of Participants Using FIX Replacement Therapy |  | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Number of Participants Remaining Free of Previous Continuous Routine FIX Prophylaxis |  | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Number of Participants With New Target Joints | Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period. | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| Percentage of Resolution of Target Joints | Target joint is defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period. | From Year 5 after administration of CSL222 in parent study up to Year 15 | 
| EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility 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 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 6 after administration of CSL222 in parent study up to Year 15 | 
| EQ-5D-5L VAS Overall Score | The EQ-5D-5L questionnaire consists of the EQ-5D-5L descriptive system and the EQ-5D VAS. The EQ-5D VAS, which measures overall health status on a vertical visual analogue scale, ranges from 0 to 100. A higher score indicates better QoL. | From Year 6 after administration of CSL222 in parent study up to Year 15 | 
| Hem-A-QoL Overall Score | The Hem-A-QoL (Hemophilia Quality of Life Questionnaire for Adults) 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 6 after administration of CSL222 in parent study up to Year 15 |