Clinical Evaluation of a Recombinant Factor VIII Preparation (Kogenate) in Previously Untreated Patients with Hemophilia A
- 166 Downloads
The safety and efficacy of a recombinant factor VIII (rFVIII) preparation (Kogenate) for the treatment of bleeding episodes was studied in previously untreated patients (PUPs) with severe, moderate, and mild hemophilia A. Patient peripheral blood samples taken at baseline and at 3, 6, 9, 12,18, and 24 months after the first infusion were evaluated for FVIII inhibitor antibodies by the Bethesda assay, for antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Samples for general laboratory testing were also drawn every 6 months after the first 24 months. Hemostatic efficacy was assessed by physicians, and adverse events were recorded throughout the study period. Forty-three PUPs (30 with FVIII:C <1%; 10 with FVIII:C 1%-5%; and 3 with FVIII:C >5%) aged 3 months to 32 years were enrolled at 33 centers in Japan. Patients were studied for a mean of 51 months (range, 11-80 months), and the mean exposure time was 83 days (range, 2-571 days). The incidence of occurrence of FVIII inhibitors was 34.9% (high responders [≥10 Bethesda U/mL], 11.6%; low responders [0.5->10 Bethesda U/mL],23.3%). The median cumulative exposure time of inhibitor detection was 12 days, indicating inhibitor development at an early stage after the start of infusion of this preparation. Hemostasis was achieved with a single dose of Kogenate in 94.8% of the 951 bleeding episodes recorded in the study. Transient increases in antibodies against baby hamster kidney proteins and antimouse immunoglobulin G were observed in 14.0% and 18.6% of patients, respectively. Anti-rFVIII seroconversion was observed in 18.6% of patients and only in patients with inhibitor antibodies. Antibody responses to trace proteins were not correlated with drug-related adverse events with the exception of FVIII activity inhibition in PUPs with anti-rFVIII seroconversion. These data indicate that Kogenate is safe and effective for the treatment of bleeding in PUPs with hemophilia A.
Key wordsRecombinant factor VIII Kogenate Clinical study Previously untreated patients with hemophilia A Inhibitor Antibody to foreign protein
Unable to display preview. Download preview PDF.
- 4.Yoshioka A. Advances in hemophilia and other coagulation disorders: recombinant factor VIII preparations.Int J Pediatr Hematol Oncol. 1994;1:491–497.Google Scholar
- 6.Fukui H, Mori K, Ishikawa M, et al. A long-term, multi-center clinical study of recombinant human factor VIII (BAY w 6240) in the treatment of hemophilia A [in Japanese].Nihon Yuketsu Gakkai Zasshi. 1991;37:593–604.Google Scholar
- 7.Kasper CK, Aledort LM, Counts RB, et al. A more uniform measurement of factor VIII inhibitors [letter].Thromb Diath Haemorrh. 1975;34:869–872.Google Scholar
- 14.Shima M. Mechanism of the inhibitor development and management in patients with hemophilia [in Japanese].Nihon Shouni Ketsueki Gakkai Zasshi. 1999;13:399–409.Google Scholar
- 15.Abe T, Igata A, Ikematsu S, et al. Multcenter clinical effect of heat- treated factor VIII (CP-8) preparation for patients with hemophilia A [in Japanese].Rinshio to Kenkyu. 1985;62:3640–3659.Google Scholar
- 17.Fujimaki M, Goto M, Miyazaki T, et al. Clinical study of FVIII concentrate highly purified by monoclonal antibodies to FVIII(RCG- 11) [in Japanese].Kiso to Rinsho. 1992;26:299–319.Google Scholar
- 18.Shima M. Hemophilia [in Japanese].Rinshoui. 2001;27:801–806.Google Scholar
- 20.Lusher JM, Arkin S, Hurst D. Recombinant FVIII (Kogenate) treatment of previously untreated patients (PUPs) with hemophilia A: update of safety, efficacy, and inhibitor development after seven study years.Thromb Haemost. 1997;77(suppl):162–163.Google Scholar
- 21.Gruppo R, Bray GL, Schroth P, Perry M, Gemperts ED. Safety and immunogenicity of recombinant factor VIII (RecombinateTM) in previously untreated patients (PUPs): a 6.5 year update.Thromb Haemost. 1997;77(suppl):162.Google Scholar