The FDA previously lifted its clinical hold of the AFFINE study in May 2022.
Pfizer and Sangamo Therapeutics have reopened enrollment in the phase 3 AFFINE study (NCT04370054) of giroctocogene fitelparvovec for the potential treatment of moderately severe to severe hemophilia A.1
Enrollment will resume across trial sites this September and dosing is expected to resume in October, with all sites predicted to be active again by the end of 2022. The companies expect to report a pivotal data readout in the first half of 2024.
“Ensuring the safety of study participants is our first priority,” Pfizer wrote in a study update.2
The FDA placed the AFFINE study on hold in November 2021 after Pfizer and Sangamo had voluntarily paused screening and dosing of participants due to Factor VIII (FVIII) activity greater than 150% in some participants.2 One such participant has since experienced below-the-knee deep vein thrombosis. Participants were treated with anticoagulants and protocols were amended to mitigate thrombotic risk. The FDA lifted its clinical hold in May 2022, but Pfizer kept the study on hold while discussing amended protocols with the agency.3
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“Pfizer was recently made aware of an event of below-the-knee deep vein thrombosis in 1 trial participant with elevated Factor VIII levels. This patient had a history of thrombotic events prior to participation in the study, which is a known risk factor for subsequent events and an exclusion criterion for participation in AFFINE,” Pfizer reported in the earnings statement.3 “The case was assessed to understand all potential contributing factors, including missed doses of investigator-prescribed direct oral anti-coagulants. The patient is reported to be doing well.”
The study has a target enrollment of 63 participants with moderately severe to severe hemophilia A who have been followed on routine prophylaxis with FVIII products in the lead-in study (NCT03587116). The study’s primary endpoint is efficacy as measured by annualized bleeding rate (ABR) over 12 months compared with ABR on FVIII replacement therapy during the lead-in study. Secondary outcome measures include FVIII activity levels, annualized infusion rate of exogenous FVIII activity, annualized FVIII consumption, joint health, patient-reported outcomes, quality-of-life measures, and adverse events (AEs) for up to 5 years after treatment.
Giroctocogene fitelparvovec uses the adeno-associated virus vector 6 (AAV6) to deliver complementary DNA for B domain deleted human FVIII. The therapy uses multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal, and vector backbone sequence to optimize liver-specific expression. The FDA has previously granted orphan drug, fast track, and regenerative medicine advanced therapy designations to the therapy while the EMA has granted orphan medicinal product designation to the therapy.