An Observational Cohort Study to Characterize the Effectiveness and Safety of HEMGENIX® in Patients With Hemophilia B

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Hemophilia B

Intervention / Treatment
-----------------
* Genetic: HEMGENIX
* Biological: Factor IX (FIX)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HEMGENIX Cohort: Treatment with commercial HEMGENIX. Have provided signed written informed consent within 3 months before or within 6 months after HEMGENIX treatment, or within 6 months of when the study is initiated at the participating site. FIX Prophylaxis Cohort: Adult patients (≥ 18 years) with hemophilia B who have consented and enrolled in ATHN Transcends Hemophilia Cohort (or a similar registry) and are receiving FIX prophylaxis therapy. Exclusion Criteria: HEMGENIX Cohort: The patient population that will be observed in this study must not have been treated with etranacogene dezaparvovec in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HEMGENIX<br>Patients with hemophilia B treated with HEMGENIX in countries where HEMGENIX is approved for commercial use. | Genetic: HEMGENIX<br>* 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.<br>* Other names: Etranacogene dezaparvovec;|
| FIX Prophylaxis<br>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. | Biological: Factor IX (FIX)<br>* FIX prophylaxis therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Rate (all bleeds) - HEMGENIX Cohort | Annualised Bleeding Rate (ABR) for all bleeds | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Rate (specified bleed types) - HEMGENIX Cohort | ABR for spontaneous, FIX-treated, traumatic, and joint bleeds | 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. | 
| Zero bleeds - HEMGENIX Cohort | Number of patients with zero bleeds | During follow-up after HEMGENIX treatment, up to 180 months | 
| Correlation analysis - HEMGENIX Cohort | Correlation analysis of ABR as a function of mean FIX activity. | Over the 6 to: 18, 24, 36, 48, 60, 72, 96, 108, 120, 132, 144, 156, 168, and 180 months after HEMGENIX treatment. | 
| Bleeding Rate - FIX Prophylaxis Cohort | ABR (total, spontaneous, FIX-treated, traumatic, and joint bleeds) | In the period Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 Months. | 
| FIX activity - HEMGENIX Cohort | Mean uncontaminated endogenous FIX activity (%) | 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. | 
| Annualized consumption of FIX replacement therapy - HEMGENIX Cohort | 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). | 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). | 
| Annualized consumption of FIX replacement therapy - FIX Prophylaxis Cohort | 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). | At Months 0 to: 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180. | 
| Number of patients remaining free of previous continuous routine prophylaxis - HEMGENIX Cohort | Number and proportion of patients remaining free of previous continuous routine prophylaxis (FIX replacement therapy) | At Months 6 to: 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 after HEMGENIX treatment. | 
| Target joints occurrence - HEMGENIX Cohort | The annualized occurrence of target joints (defined as 3 or more spontaneous bleeding events into a single joint within a consecutive 6-month period). | 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). | 
| Target joints resolution - HEMGENIX Cohort | 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). | During the follow-up period, up to 180 months | 
| Target joints - FIX Prophylaxis Cohort | The annualized occurrence of target joints | From Months 0 to 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180. | 
| Related Serious Adverse Events (SAEs) - number | Incidence (number) of related SAEs | During 15 years of follow-up | 
| Related SAEs - percent | Incidence (percent) of related SAEs | During 15 years of follow-up | 
| Adverse Events of Special Interest (AESIs) - number | Incidence (number) of AESIs | During 15 years of follow-up | 
| AESIs - percent | Incidence (percent) of AESIs | During 15 years of follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemophilia B, HEMGENIX