Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: A randomized controlled trial

Erich V. de Paula, Kaan Kavakli, Johnny Mahlangu, Yasmin Ayob, Steven R. Lentz, Massimo Morfini, L. Nemes, Silva Z. Šalek, Midori Shima, Jerzy Windyga, Silke Ehrenforth, Ampaiwan Chuansumrit

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Summary. Background:A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors. Patients/Methods:This global, prospective, randomized, double-blinded, active-controlled, dose-escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80μgkg-1 with one to three doses of recombinant FVIIa (rFVIIa) at 90μgkg-1 in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy. Results and Conclusions:Overall, 96 joint bleeds in 51 patients (>12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98% of bleeds were controlled within 9h of the initial dose in a combined evaluation of 20-80μgkg-1 vatreptacog alfa. The efficacy rate observed for rFVIIa (90%) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00486278).

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Hemophilia A
Randomized Controlled Trials
Joints
Therapeutics
recombinant FVIIa
vatreptacog alfa
Pharmacokinetics
Clinical Trials

Keywords

  • Hemophilia
  • Inhibitors
  • RFVIIa analog
  • Safety
  • Vatreptacog alfa (activated)

ASJC Scopus subject areas

  • Hematology

Cite this

Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors : A randomized controlled trial. / de Paula, Erich V.; Kavakli, Kaan; Mahlangu, Johnny; Ayob, Yasmin; Lentz, Steven R.; Morfini, Massimo; Nemes, L.; Šalek, Silva Z.; Shima, Midori; Windyga, Jerzy; Ehrenforth, Silke; Chuansumrit, Ampaiwan.

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 1, 01.2012, p. 81-89.

Research output: Contribution to journalArticle

de Paula, EV, Kavakli, K, Mahlangu, J, Ayob, Y, Lentz, SR, Morfini, M, Nemes, L, Šalek, SZ, Shima, M, Windyga, J, Ehrenforth, S & Chuansumrit, A 2012, 'Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: A randomized controlled trial', Journal of Thrombosis and Haemostasis, vol. 10, no. 1, pp. 81-89. https://doi.org/10.1111/j.1538-7836.2011.04549.x
de Paula, Erich V. ; Kavakli, Kaan ; Mahlangu, Johnny ; Ayob, Yasmin ; Lentz, Steven R. ; Morfini, Massimo ; Nemes, L. ; Šalek, Silva Z. ; Shima, Midori ; Windyga, Jerzy ; Ehrenforth, Silke ; Chuansumrit, Ampaiwan. / Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors : A randomized controlled trial. In: Journal of Thrombosis and Haemostasis. 2012 ; Vol. 10, No. 1. pp. 81-89.
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abstract = "Summary. Background:A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors. Patients/Methods:This global, prospective, randomized, double-blinded, active-controlled, dose-escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80μgkg-1 with one to three doses of recombinant FVIIa (rFVIIa) at 90μgkg-1 in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy. Results and Conclusions:Overall, 96 joint bleeds in 51 patients (>12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98{\%} of bleeds were controlled within 9h of the initial dose in a combined evaluation of 20-80μgkg-1 vatreptacog alfa. The efficacy rate observed for rFVIIa (90{\%}) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov (Registration Number: NCT00486278).",
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AU - de Paula, Erich V.

AU - Kavakli, Kaan

AU - Mahlangu, Johnny

AU - Ayob, Yasmin

AU - Lentz, Steven R.

AU - Morfini, Massimo

AU - Nemes, L.

AU - Šalek, Silva Z.

AU - Shima, Midori

AU - Windyga, Jerzy

AU - Ehrenforth, Silke

AU - Chuansumrit, Ampaiwan

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