Back to Search
Start Over
Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa
- Source :
- Journal of Thrombosis and Haemostasis
- Publication Year :
- 2014
- Publisher :
- BlackWell Publishing Ltd, 2014.
-
Abstract
- Background Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. Objectives To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. Patients and methods In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept™2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg−1) or rFVIIa (one to three doses at 90 μg kg−1). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. Results In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24–48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. Conclusions This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit–risk profile is unlikely to be achieved with vatreptacog alfa.
- Subjects :
- Adult
Male
medicine.medical_specialty
Adolescent
Factor VIIa
Pharmacology
Hemophilia A
law.invention
Clinical Haemostasis and Thrombosis
Young Adult
clinical trial, phase III
Randomized controlled trial
Double-Blind Method
law
hemophilia
inhibitors
recombinant factor VIIa
Medicine
antibodies
Humans
Child
Aged
Cross-Over Studies
biology
business.industry
Hematology
Turoctocog alfa
Middle Aged
Recombinant Proteins
Surgery
Recombinant factor VIIa
Recombinant DNA
biology.protein
business
Subjects
Details
- Language :
- English
- ISSN :
- 15387836 and 15387933
- Volume :
- 12
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....2cda7dc222225026f6ef334db58bc053