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 V IIa (rFVIIa) was conducted in Japanese patients with severe hemophilia A or B with inhibitors. The trial consisted of 2 parts. In study 1, the pharmac okinetics pharmacodynamics, and safety of a single dose of 120 mug/kg of rF VIIa were investigated in 8 patients. In the subsequent study 2, the hemost atic 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 re turned 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 partia l thromboplastin time and prothrombin time in the patients were immediately shortened but returned to the baseline within 24 hours after dosing. In st udy 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 episod es were treated excellently or effectively, with 5 (3.2%) ineffective episo des. There was no apparent trend in the relationship of the hemostatic effe ct with bleeding sites, mean dose, or number of injections, The efficacy ra te, however, was significantly higher (90.0%) in bleeding episodes treated within 3 hours than in those treated at longer intervals (31.0%). No treatm ent-related adverse events were observed, and there was no evidence of anti body formation to rFVIIa. In conclusion, rFVIIa is an effective and well-to lerated option for treatment of bleeding episodes in hemophilia patients wi th inhibitors. Int J Hematol. 2001;73:517-525. (C) 2001 The Japanese Societ y of Hematology.