PERSEPT 1: a phase 3 trial of activated eptacog beta for on-demand treatment of haemophilia inhibitor-related bleeding - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Haemophilia Année : 2017

PERSEPT 1: a phase 3 trial of activated eptacog beta for on-demand treatment of haemophilia inhibitor-related bleeding

M. Wang
  • Fonction : Auteur
J. Lawrence
  • Fonction : Auteur
D. Quon
  • Fonction : Auteur
J. Ducore
  • Fonction : Auteur
L. Simpson
  • Fonction : Auteur
L. Boggio
  • Fonction : Auteur
I. Mitchell
  • Fonction : Auteur
G. Yuan
  • Fonction : Auteur
W. Alexander
  • Fonction : Auteur

Résumé

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.

Domaines

Hématologie

Dates et versions

hal-01757551 , version 1 (03-04-2018)

Identifiants

Citer

M. Wang, J. Lawrence, D. Quon, J. Ducore, L. Simpson, et al.. PERSEPT 1: a phase 3 trial of activated eptacog beta for on-demand treatment of haemophilia inhibitor-related bleeding. Haemophilia, 2017, 23 (6), pp.832 - 843. ⟨10.1111/hae.13301⟩. ⟨hal-01757551⟩
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