A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Biological: SB-525 (PF-07055480)
- Registration Number
- NCT03061201
- Lead Sponsor
- Pfizer
- Brief Summary
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)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 13
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Sequential dose escalation SB-525 (PF-07055480) SB-525 (PF-07055480) is administered as a single infusion
- Primary Outcome Measures
Name Time Method Changes in circulating FVIII activity Up to 5 years after SB-525 (PF-07055480) infusion Incidence of adverse events and serious adverse events Up to 5 years after SB-525 (PF-07055480) infusion
- Secondary Outcome Measures
Name Time Method
Related Research Topics
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Trial Locations
- Locations (22)
UPMC Montefiore Clinical and Translational Research Center
🇺🇸Pittsburgh, Pennsylvania, United States
City of Hope Medical Center
🇺🇸Duarte, California, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Hemophilia Center of Western PA
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC, Investigational Drug Service
🇺🇸Pittsburgh, Pennsylvania, United States
Washington Institute for Coagulation
🇺🇸Seattle, Washington, United States
University of California, San Francisco - Investigational Drug Service (IDS) Pharmacy
🇺🇸San Francisco, California, United States
Vanderbilt Hemostasis-Thrombosis Clinic
🇺🇸Nashville, Tennessee, United States
University of California, San Francisco - Outpatient Hematology Clinic
🇺🇸San Francisco, California, United States
University of California, San Francisco -Moffitt Hospital
🇺🇸San Francisco, California, United States
University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Vanderbilt University Medical Center Clinical Research Center
🇺🇸Nashville, Tennessee, United States
Vanderbilt Hemostasis Treatment Clinic
🇺🇸Nashville, Tennessee, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Midtown Ambulatory Care Center
🇺🇸Sacramento, California, United States
UC Davis Ambulatory Care Clinic
🇺🇸Sacramento, California, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
UC Davis CTSC Clinical Research Center
🇺🇸Sacramento, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
USF Health Morsani Center For Advanced Healthcare
🇺🇸Tampa, Florida, United States
UC Davis Hemophilia Treatment Center
🇺🇸Sacramento, California, United States
UC Davis Investigational Drug Services Pharmacy
🇺🇸Sacramento, California, United States