Long-term Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec in Patients with Hemophilia A or Hemophilia B: A Phase 3 Cohort Study

The primary objective is to characterize the long-term safety of participants with hemophilia A or hemophilia B who have received prior treatment with giroctocogene fitelparvovec or fidanacogene elaparvovec. Additionally, the study aims to describe the durability of transgene expression following these treatments. Secondary objectives include:

• Assessment of clinical outcomes related to the administered therapies.
• Further evaluation of the long-term safety profile.
• Evaluation of the impact on quality of life and physical function.

The study population consists of 155 male patients. The cohort includes individuals diagnosed with hemophilia A or severe to moderately severe hemophilia B, characterized by FIX:C levels of ≤ 2%. Participants must have previously received administration of giroctocogene fitelparvovec or fidanacogene elaparvovec within a prior study sponsored by Pfizer. The objectives of the study are:

• To characterize the long-term safety of participants following prior treatment with giroctocogene fitelparvovec or fidanacogene elaparvovec.
• To describe the durability of transgene expression for giroctocogene fitelparvovec or fidanacogene elaparvovec.

This Phase 3, multi-country cohort study is designed to describe the long-term safety and effectiveness of a prior single-dose treatment with giroctocogene fitelparvovec or fidanacogene elaparvovec. The study focuses on participants previously treated with these agents for hemophilia A or hemophilia B. The primary objectives are to characterize long-term safety and describe the durability of transgene expression. Key primary endpoints include the incidence of thromboembolic events, factor inhibitor development, hepatic malignancy, liver abnormalities, and factor activity level. Secondary endpoints involve annualized bleeding rate, consumption of exogenous factor, and all-cause mortality. The study is expected to occur between July 2026 and February 2040.

Fidanacogene elaparvovec is an investigational solution for infusion administered via intravenous use at a dosage of 500,000,000,000 vector genomes (vg)/mL. This substance is utilized in the context of participants with hemophilia A.

Giroctocogene fitelparvovec is an investigational solution for infusion administered at a dosage of 30,000,000,000,000 vector genomes (vg)/mL. This orphan drug is utilized in the context of participants with hemophilia B.

The assessment of effectiveness in this study focuses on the durability of transgene expression following prior treatment with giroctocogene fitelparvovec or fidanacogene elaparvovec. The primary efficacy parameter is the factor activity level.

Secondary efficacy parameters include:

• Annualized Bleeding Rate (ABR), comprising both treated and untreated instances;
• Annualized Inhibitor Rate (AIR) of exogenous factor;
• Consumption of exogenous factor;
• Incidence of and time from the previously administered gene therapy infusion to the resumption of prophylaxis;
• EQ-5D-5L dimension and visual analogue scale (VAS) scores.