Yazarlar : Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, Li E, Jiang H, Li L, Dumont JA, Goyal J, Zhang X, Sommer J, McCue J, Barbetti M, Luk A, Pierce GF.

Yayın : Blood.

Yayın Yılı : 2012

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22223821

Konu : Hemofili

Literatür İçeriği :  

Abstract

Current factor VIII (FVIII) products display a half-life (t(1/2)) of approximately 8-12 hours, requiring frequent intravenous injections for prophylaxis andtreatment of hemophilia A patients. rFVIIIFc is a recombinant fusion protein composed of a single molecule of FVIII covalently linked to the Fc domain of human IgG(1) to extend circulating rFVIII half-life. This first-in-human study in previously-treated subjects with severe hemophilia A investigated safety and pharmacokinetics of rFVIIIFc. Sixteen subjects received a single dose of Advate(®) at 25 or 65 IU/kg followed by an equal dose of rFVIIIFc. Most adverse events were unrelated to study drug. None of the study subjects developed anti rFVIIIFc antibodies or inhibitors. Across dose levels, as compared with Advate, rFVIIIFc showed 1.5 to 1.7-fold longer elimination t(1/2), 1.49 to 1.56-fold lower clearance, and 1.48 to 1.56-fold higher total systemic exposure. Advate and rFVIIIFc had comparable dose-dependent peak plasma concentrations and recoveries. Time to 1% FVIII activity above baseline was approximately 1.53 to 1.68 fold longer than Advate across dose levels. Each subject demonstrated prolonged exposure to rFVIIIFc relative to Advate. Thus, rFVIIIFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia A. Trial registered at www.clinicaltrials.gov (NCT01027377).

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