Yazarlar : Shapiro AD, Ragni MV, Valentino LA, Key NS, Josephson NC, Powell JS, Cheng G, Thompson AR, Goyal J, Tubridy KL, Peters RT, Dumont JA, Euwart D, Li L, Hallén B, Gozzi P, Bitonti AJ, Jiang H, Luk A, Pierce GF.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22110246

Konu : Hemofili

Literatür İçeriği :  

Abstract

Current Factor IX (FIX) products display a half-life (t(1/2)) of approximately 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in hemophilia B patients. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics (PK) of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG(1), to extend circulating time. Fourteen subjects received a single dose of rFIXFc: one subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated and most AEs were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and antigen exposure were observed. Utilizing baseline subtraction, mean activity terminal t(1/2) and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is approximately 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.

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