A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objective of the study will evaluate the annualized bleeding rate [ABR] for participants treated with gene therapy versus standard of care (SOC) therapy (FIX prophylaxis replacement regimen).

Official Title
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Phase 3, Open-label, Single-arm Study to Evaluate Efficacy and Safety of FIX Gene Transfer With PF-06838435 (rAAV-Spark100-hFIX-R338L) in Adult Male Participants With Moderately Severe to Severe Hemophilia B (FIX:C ≤2%) (BeneGene-2)

Conditions
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Hemophilia B

Intervention / Treatment
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* Biological: PF-06838435/ fidanacogene elaparvovec


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males who completed 6 months of Factor IX prophylaxis therapy during the lead-in study (C0371004) prior to providing consent at the screening visit for this study. Documented moderately severe to severe hemophilia B (Factor IX activity < =2%) Previous experience with FIX therapy (=>50 documented exposure days to a FIX protein product) Suspension of prophylaxis therapy for hemophilia B after administration of the study drug Laboratory values (hemoglobin, platelets and creatinine) within study specified limits Agree to contraception until components of the drug are eliminated from their body Capable of giving signed informed consent Exclusion Criteria Anti-AAVRh74var neutralizing antibodies (nAb) titer above the established threshold (ie, positive for nAb). History of inhibitor to Factor IX or inhibitor detected during screening. Clinical signs or symptoms of decreased response to Factor IX Hypersensitivity to Factor IX replacement product or IV immunoglobulin administration History of chronic infection or other chronic disease Any conditions associated with increased thromboembolic risk Concurrent clinically significant major disease or condition unsuitable for participation and/or may interfere with the interpretation of study results Laboratory values at screening visit that are abnormal or outside acceptable study limits Current unstable liver or biliary disease Currently on antiviral therapy for hepatitis B or C Planned surgical procedure requiring Factor IX surgical prophylactic factor treatment 15 months from screening visit Use of restricted therapies (e.g., blood products, acetylsalicylic acid [aspirin] or ibuprofen, other investigational therapy, and by-passing agents) Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 12 weeks of screening visit Active hepatitis B or C; hepatitis B surface antigen, hepatitis B virus deoxyribonucleic acid positivity, or hepatitis C virus ribonucleic acid positivity Significant liver disease Serological evidence of HIV1 or HIV2 infection with either CD4+ cell count <=200 mm3 and/or a viral load >20 copies/mL Study and sponsor staff involved in the conduct of the study and their families Unable to comply with study procedures Sensitivity to heparin or heparin induced thrombocytopenia Sensitivity to any of the study interventions, or components thereof, or drug or other allergy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-06838435/ fidanacogene elaparvovec<br> | Biological: PF-06838435/ fidanacogene elaparvovec<br>* Gene Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleeding rate (ABR) for total bleeds |  | Week 12 to Month 15 post PF-06838435 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleeding rate (ABR) for treated bleeds |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Annualized infusion rate (AIR) of exogenous Factor IX |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Vector derived Factor IX activity (FIX:C) level at steady state |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Factor IX consumption |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Frequency of target joint bleeds |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Percentage of the participants without bleeds |  | Week 12 to Month 15 post PF-06838435 infusion | 
| Change in joint health as measured by the Hemophilia Joint Health Score (HJHS) instrument |  | 12 months post PF-06838435 infusion | 
| Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL) Physical Health domain |  | 12 months post PF-06838435 infusion | 
| Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score |  | 12 months post PF-06838435 infusion | 
| Annualized Bleeding Rate for total bleeds |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Vector-derived FIX:C level by study visit and the geometric mean at each yearly interval |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Annualized infusion rate (AIR) of exogenous Factor IX |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| ABR for treated bleeds |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Annualized Factor IX consumption |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Annualized number of bleeding events of specific type: spontaneous and traumatic, and untreated |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Hemophilia Joint Health Score (HJHS) |  | Annually for 6 years | 
| Frequency of target joint bleeds |  | From Month 15 to Month 24, by yearly intervals after 24 months, and across 6 years of follow-up | 
| Patient Reported Outcome (PRO) instrument - Hemophilia Quality of Life (Haem A QoL) Physical Health domain |  | Annually for 6 years | 
| Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score |  | Annually for 6 years | 
| Incidence and severity of all adverse events collected during the study |  | For the duration of 6 years after PF-06838435 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FIX, PF 06838435, Hemophilia, Hemophilia B, Factor IX, Gene Therapy, Infusion, rAAV Spark100 hFIX Padua, rAAV Spark100-hFIX-R338L, R338L, BeneGene 2, Hematological Diseases, Annualized bleeding rate (ABR)