Targeting 1-3% and 8-12% FVIII troughs was efficacious, with fewer bleeds in the 8-12% arm; safety profiles in both arms were similar.
Rurioctocog alfa pegol consumption varied widely in each arm with overlapping ranges, emphasizing the need for personalized treatment.
Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% is efficacious and well-tolerated in people with hemophilia A (PwHA). As some may benefit from higher FVIII troughs, the PROPEL trial compared safety and efficacy of 2 target FVIII trough levels in PwHA with severe disease, aged 12-65 years, annualized bleeding rate ≥2, and previous FVIII treatment. They were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1-3% (reference arm) or 8-12% (elevated arm). Treatment-adjustment period was in the first 6 months. Primary endpoint: proportion of PwHA (full analysis set [FAS]) with zero total bleeds (all bleeds) during second 6 months. Overall, 115 male PwHA were randomized (N=115, FAS; N=95, per-protocol analysis set [PPAS]). In the 1-3% and 8-12% arms, respectively, point estimates (95% CI) of proportions of PwHA with zero total bleeds were 42% (29-55%) and 62% (49-75%) in FAS (P=0.055) and 40% (27-55%) and 67% (52-81%) in PPAS (P=0.015). Dosing frequency and consumption varied widely in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA. Serious AEs occurred in 7/115 (6%) PwHA, including 1 treatment-related serious AE in 8-12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms, with no new safety signal in the 8-12% arm vs previous studies. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and also emphasize the importance of personalized treatment. Trial registration: www.ClinicalTrials.gov (#NCT02585960).