PERSEPT 1: a phase 3 trial of activated eptacog beta for on‐demand treatment of haemophilia inhibitor‐related bleeding. Issue 6 (3rd August 2017)

• Record Type: Journal Article
• Authors: Wang, M.; Lawrence, J. B.; Quon, D. V.; Ducore, J.; Simpson, M. L.; Boggio, L. N.; Mitchell, I. S.; Yuan, G.; Alexander, W. A.; Schved, J.‐F.
• Is Part Of: Haemophilia. Volume 23:Issue 6(2017)
• Page Start: 832
• Page End: 843
• Publication Date: 2017-08-03
• Subjects: bypassing agent -- clinical trial -- haemophilia A or B -- haemorrhage -- inhibitors -- PERSEPT 1 -- rFVIIa; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.13301
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract : Introduction: Haemophilia A or B patients with inhibitors have been treated with 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 haemostasis. 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, cross‐over study of 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 within 12 hours, determined by a composite of objective and pain measures. In the 75 μg/kg IDR, 84.9% (95% 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 haemostasis as a treatment goal for clinicians who treat haemorrhage in the inhibitor population.