PERSEPT 1
Abstract
INTRODUCTION:
Haemophilia A or B patients with inhibitors have been treated with Factor VIIa (FVIIa)-containing bypassing agents for over 20 years. However, due to uncertainty regarding dose response and thrombotic risk, the use of a gradual, titrated, minimal dosing strategy remains prevalent, potentially hampering early hemostasis.
AIM:
Evaluate the dose-dependent efficacy, safety, and immunogenicity of activated eptacog beta (rhFVIIa)—a new recombinant inhibitor bypassing agent for the treatment of bleeding episodes (BEs).
METHODS:
A Phase 3, randomized, crossover study of two Initial Dose Regimens (IDRs) in 27 bleeding congenital haemophilia A or B subjects with inhibitors was conducted to evaluate on-demand treatment of mild/moderate BEs. Intravenous 75 μg/kg or 225 μg/kg initial doses with 75 μg/kg subsequent doses by schedule were administered until clinical response.
RESULTS:
The primary endpoint was sustained clinical response 12 hours following initiation of treatment, determined by a composite of objective and patient-reported indicators of clinical response. In the 75 μg/kg IDR, 84.9% (95% confidence interval [CI]; 74.0%, 95.7%) of mild/moderate BEs at 12 hours were successfully treated compared to 93.2% (95% CI; 88.1%, 98.3%) treated in the 225 μg/kg IDR. Efficacy between the IDRs was statistically different (P<.020) in mild/moderate bleeding episodes. Both IDRs were well tolerated with no detectable immunogenic or thrombotic responses to rhFVIIa or host cell proteins.
CONCLUSION:
The dose-dependent efficacy seen in this study supports individualizing the initial dose of eptacog beta to optimize clinical response. By reducing uncertainty, the PERSEPT 1 results should increase the adoption of early hemostasis as a treatment goal for clinicians who treat haemorrhage in the inhibitor population.
To access the peer-reviewed article, visit https://onlinelibrary.wiley.com/doi/10.1111/hae.13301/epdf
To learn more about this trial visit: clinicaltrials.gov
