PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors.

Abstract

INTRODUCTION:

Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.

AIM:

To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3.

METHODS:

Subjects were administered 200 µg/kg (major procedures) or 75 µg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75 µg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period.

RESULTS:

Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI: 47.8%-100%) for minor procedures and 66.7% (95% CI: 22.3%-95.7%) for major procedures; 81.8% (95% CI: 48.2%-97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported.

CONCLUSION:

Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.

• Authors: Miguel Escobar, James Luck, Yevhenii Averianov, Jonathan Ducore, Maria Fernanda López Fernández, Adam Giermasz, Daniel P Hart, Janna Journeycake, Craig Kessler, Cindy Leissinger, Johnny Mahlangu, Laura Villarreal Martinez, Wolfgang Miesbach, Ismail Haroon Mitha, Doris Quon, Mark T Reding, Jean-François Schved, Oleksandra Stasyshyn, Kateryna V Vilchevska, Michael Wang, Jerzy Windyga, W Allan Alexander, Ahmad Al-Sabbagh, Daniel Bonzo, Ian S Mitchell, Thomas A Wilkinson, Cédric Hermans
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 27 Issue 6 Pg. 911-920 (Nov 2021) ISSN: 1365-2516 [Electronic] England
• PMID: 34614267 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.

Chemical References

• Hemostatics
• Recombinant Proteins
• recombinant FVIIa
• Factor VIIa

Topics

• Factor VIIa
• Hemophilia A (drug therapy)
• Hemostasis
• Hemostatics (therapeutic use)
• Humans
• Perioperative Care
• Recombinant Proteins