Brief Title
A Study of Recombinant AAV2/6 Human Factor 8 Gene Therapy SB-525 (PF-07055480) in Subjects With Severe Hemophilia A
Official Title
A PHASE 1/2, OPEN-LABEL, ADAPTIVE, DOSE-RANGING STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF SB-525 (PF-07055480) (RECOMBINANT AAV2/6 HUMAN FACTOR 8 GENE THERAPY) IN ADULT SUBJECTS WITH SEVERE HEMOPHILIA A
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Incidence of adverse events and serious adverse events
Condition
Hemophilia A
Intervention
SB-525 (PF-07055480)
Study Arms / Comparison Groups
Sequential dose escalation
Description: SB-525 (PF-07055480) is administered as a single infusion
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
11
Start Date
June 21, 2017
Completion Date
July 23, 2024
Primary Completion Date
July 23, 2024
Eligibility Criteria
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
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Pfizer CT.gov Call Center, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03061201
Organization ID
SB-525-1603
Secondary IDs
C3731001
Responsible Party
Sponsor
Study Sponsor
Pfizer
Study Sponsor
Pfizer CT.gov Call Center, Study Director, Pfizer
Verification Date
September 2022