title: Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients.
abstract: Current factor IX (FIX) products display a half-life (t(1/2)) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics 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; 1 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 adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t(1/2) and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 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.
authors: Indiana Hemophilia and Thrombosis Center, Indianapolis, 46260, USA. ashapiro@ihtc.org
authors: Amy D
authors: AD
authors: Shapiro
authors: Margaret V
authors: MV
authors: Ragni
authors: Leonard A
authors: LA
authors: Valentino
authors: Nigel S
authors: NS
authors: Key
authors: Neil C
authors: NC
authors: Josephson
authors: Jerry S
authors: JS
authors: Powell
authors: Gregory
authors: G
authors: Cheng
authors: Arthur R
authors: AR
authors: Thompson
authors: Jaya
authors: J
authors: Goyal
authors: Karen L
authors: KL
authors: Tubridy
authors: Robert T
authors: RT
authors: Peters
authors: Jennifer A
authors: JA
authors: Dumont
authors: Donald
authors: D
authors: Euwart
authors: Lian
authors: L
authors: Li
authors: Bengt
authors: B
authors: Hallén
authors: Peter
authors: P
authors: Gozzi
authors: Alan J
authors: AJ
authors: Bitonti
authors: Haiyan
authors: H
authors: Jiang
authors: Alvin
authors: A
authors: Luk
authors: Glenn F
authors: GF
authors: Pierce
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005164:Factor IX / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D002836:Hemophilia B / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012449:Safety; D055815:Young Adult
chemical_list: D011993:Recombinant Fusion Proteins; D005164:Factor IX