Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults

Study Overview
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Brief Summary
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C3731003 is a pivotal Phase 3 study to evaluate the clinical efficacy and safety of a single IV infusion of PF-07055480 / giroctocogene fitelparvovec (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in adult male participants with moderately severe or severe hemophilia A (FVIII:C≤1%) for the study duration of 5 years. The study will enroll eligible participants who have been followed on routine prophylaxis with FVIII products in the Lead-In study C0371004.

Official Title
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Phase 3, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of PF-07055480 (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in Adult Male Participants With Moderately Severe to Severe Hemophilia A(FVIII:C≤1%)

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy


Participation Criteria
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Eligibility Criteria
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Main inclusion Criteria Males who have been followed on routine Factor VIII prophylaxis therapy during the lead-in study (C0371004) and have > = 150 documented exposure days to a Factor VIII protein product Moderately severe to severe hemophilia A (Factor VIII activity < =1%) Suspension of FVIII prophylaxis therapy post study drug infusion Main exclusion Criteria Anti-AAV6 neutralizing antibodies History of inhibitor to Factor VIII Laboratory values at screening visit that are abnormal or outside acceptable study limits Significant and/or unstable liver disease, biliary disease, significant liver fibrosis Conditions associated with increased thromboembolic risk such as inherited or acquired thrombophilia, or a history of thrombotic events Planned surgical procedure requiring Factor VIII surgical prophylactic factor treatment 12 months from screening visit Active hepatitis B or C Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 and/or viral load >20 copies/mL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07055480 (giroctocogene fitelparvovec)<br>Single administration of PF-07055480 | Biological: PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy<br>* Single IV infusion<br>* Other names: Gene Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total annualized bleeding rate (ABR) |  | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FVIII activity levels |  | 15 months | 
| Annualized bleeding rate (ABR) |  | 15 months | 
| Annualized infusion rate (AIR) of exogenous Factor VIII Activity |  | 15 months | 
| Annualized FVIII consumption |  | 15 months | 
| Annualized bleeding rate (ABR) and total ABR of specific type by cause and by location |  | 15 months | 
| Change in joint health using HJHS (Hemophilia Joint Health Score) | HJHS is a validated outcome tool developed for the assessment of joint health in people with hemophilia. The ordinal joint score assesses 9 items in 6 index joints. | Yearly up to 5 years | 
| Patient Reported Outcome (PRO) instrument - Hemophilia Activities List (HAL) | HAL is a disease specific measure of the impact of hemophilia on functional abilities in adults. The instrument consists of 42 items across 7 domains, utilizing a past month recall period. Each item is rated on a scale of 0-6 with higher recoded scores indicating more functional limitations. | Yearly up to 5 years | 
| Patient Reported Outcome (PRO) instrument - Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) | Haem-A-QoL is a disease specific measure of health-related quality of life in patients with hemophilia. Intended for adults, the instrument uses a 4-week recall period to assess health across 10 domains consisting of 46 items. Each item is rated on a scale of 0-6 with lower scores indicating better health-related quality of life. | Yearly up to 5 years | 
| Incidence and severity of AEs |  | 5-year study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SB-525, Hemophilia, Factor VIII, FVIII, Gene Therapy, AAV, AAV6, Annualized bleeding rate, ABR, giroctocogene fitelparvovec, AFFINE, PF-07055480