A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A
Purpose
The purpose of the study is to evaluate the safety, tolerability and time-course profile of FVIII activity after dosing with SB-525 (PF-07055480)
Condition
- Hemophilia A
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male ≥18 years of age - Severe hemophilia A (past evidence of circulating FVIII activity of < 1% normal) - Treated or exposed to FVIII concentrates or cryoprecipitate for at least 150 exposure days - ≥12 bleeding episodes if receiving on-demand therapy over the preceding 12 months - Agree to use double barrier contraceptive until at least 3 consecutive semen samples are negative for AAV 2/6 after SB-525 infusion
Exclusion Criteria
- Presence of neutralizing antibodies - Current inhibitor, or history of FVIII inhibitor (except for transient low titer inhibitor detected in childhood) - History of hypersensitivity response to FVIII - History of Hepatitis B or HIV-1/2 infection - History of Hepatitis C, unless viral assays in two samples, collected at least 6 months apart, are negative - Evidence of any bleeding disorder in addition to hemophilia A - Markers of hepatic inflammation or overt or occult cirrhosis - History of chronic renal disease or creatinine ≥ 1.5 mg/dL - Presence of liver mass on magnetic resonance imaging (MRI), or, positive alpha fetoprotein - Presence of > grade 2 liver fibrosis on elastography for subjects with history of treated Hepatitis C or suspicion of chronic liver disease
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Dose selection based on safety and kinetics of circulating FVIII levels observed in previously dosed participants.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- Open Label
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Sequential dose escalation |
SB-525 (PF-07055480) is administered as a single infusion |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Pfizer
Study Contact
Detailed Description
The proposed clinical study uses a recombinant adeno-associated virus 2/6 (AAV2/6) vector encoding the cDNA for the B-domain deleted human F8 (hF8). The secreted FVIII has the same amino acid sequence as approved recombinant anti hemophilic factors (Refacto® and Xyntha®). The SB-525 (PF-07055480) vector encodes a liver-specific promotor module and AAV2/6 exhibits liver tropism, thus providing the potential for long-term hepatic production of FVIII in hemophilia A subjects. The constant production of FVIII after a single SB-525 (PF-07055480) administration may provide potential benefit in durable protection against bleeding and the complications thereof without lifelong repetitive IV factor replacement administration.