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


  • Presented in abstract form at the 52nd annual meeting of the American Society of Hematology, Orlando, FL, 6 December 2010. E. de Paula, K. Kavakli, J. Mahlangu, et al.; on behalf of the 1804 (ADEPT-1) Investigators. Safety and preliminary efficacy of recombinant activated FVII analog (NN1731) in the treatment of joint bleeds in congenital hemophilia patients with inhibitors. Blood 2010; 116(21): 719.

Erich de Paula, Laboratorio de Hemostasia, Hemocentro de Campinas, Rua Carlos Chagas 480, São Paulo 13081-878, Brazil.
Tel.: +55 19 3521 8756; fax: +55 19 3521 8600.


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 80 μg kg−1 with one to three doses of recombinant FVIIa (rFVIIa) at 90 μg kg−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 9 h of the initial dose in a combined evaluation of 20–80 μg kg−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 (Registration Number: NCT00486278).