Clinical trial to investigate the pharmacokinetics, pharmacodynamics, safety, and efficacy of recombinant factor VIIa in Japanese patients with hemophilia with inhibitors

A multicenter and open-labeled clinical trial of human recombinant factor VIIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmacokinetics pharmacodynamics, and safety of a single dose of 120 mug/kg of rFVIIa were investigated in 8 patients. In the subsequent study 2, the hemostatic effect and safely of rFVIIa were evaluated during a 24-week period in 10 patients. In study I, the mean maximum FVII-coagulant activity (FVII:C) was found to occur after 10 minutes; activity then decreased rapidly and returned to the baseline within 24 hours after a single intravenous infusion of rFVIIa. The mean half-life of FVII:C was 3.5 hours. The activated partial thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In study 2, 86 mug/kg to 120 mug/kg of rFVIIa (mean, 97 mug/kg) was administered 1 to 85 times to 10 patients. A total of 58.0% (91/157) of bleeding episodes were treated excellently or effectively, with 5 (3.2%) ineffective episodes. There was no apparent trend in the relationship of the hemostatic effect with bleeding sites, mean dose, or number of injections, The efficacy rate, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatment-related adverse events were observed, and there was no evidence of antibody formation to rFVIIa. In conclusion, rFVIIa is an effective and well-tolerated option for treatment of bleeding episodes in hemophilia patients with inhibitors. Int J Hematol. 2001;73:517-525. (C) 2001 The Japanese Society of Hematology.