PB0634 - A Phase 3, single-arm, multicenter, open-label, one-way crossover study to evaluate the efficacy and safety of fitusiran prophylaxis in people with severe hemophilia A or B, with or without inhibitors

Background: Fitusiran, an investigational, subcutaneous prophylactic siRNA therapeutic, targets antithrombin (AT) with the goal of rebalancing hemostasis in people with hemophilia A or B, with or without inhibitors. In previous Phase 3 studies (ATLAS-INH, ATLAS-A/B and ATLAS-PPX), fitusiran 80 mg once monthly (QM) prophylaxis demonstrated a significant reduction in annualized bleeding rate (ABR) and improvements in quality of life.

Aims: ATLAS-NEO (NCT05662319) aims to further evaluate the efficacy and safety of fitusiran with revised doses and dose regimen, designed to target AT activity levels of 15–35% and enhance the benefit-risk profile of fitusiran.

Methods: ATLAS-NEO is a multicentre (approximately 60 sites), multinational, open-label, single-arm, one-way crossover, Phase 3 study, enrolling approximately 75 males aged ≥12 years with severe hemophilia A or B, with or without inhibitors who are fitusiran naïve and have switched from prior clotting factor concentrate (CFC) or bypassing agent (BPA) prophylaxis or on-demand standard of care (SoC). Participants must be willing and able to provide written informed consent prior to enrolment. This study consists of a screening period of approximately 60 days, a 6-month standard of care period in which participants continue their prior CFC/BPA regimen, and a 36-month treatment period where participants receive fitusiran prophylaxis, beginning with a dose of 50 mg once every two months (Q2M; Figure). To target AT activity levels of 15–35%, possible fitusiran dose adjustments include 20 mg Q2M or QM; 50 mg Q2M or QM and 80 mg QM. The primary objective is to characterize the frequency of treated bleeding episodes with fitusiran prophylaxis. Key secondary objectives evaluate the efficacy of fitusiran prophylaxis versus prophylaxis or on-demand SoC. The primary endpoint is ABR during the 12-month primary efficacy period from Month 6 to Month 18; secondary endpoints are listed in the Table.

Results: Not applicable.

Conclusion(s): Not applicable.