Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

Elena Santagostino, Claude Negrier, Robert Klamroth, Andreas Tiede, Ingrid Pabinger-Fasching, Christine Voigt, Iris Jacobs, Massimo Morfini

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatmentrelated adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440.

Original languageEnglish
Pages (from-to)2405-2411
Number of pages7
JournalBlood
Volume120
Issue number12
DOIs
Publication statusPublished - Sep 20 2012

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Recombinant Fusion Proteins
Hemophilia B
Factor IX
Pharmacokinetics
Albumins
Safety
Half-Life
Plasmas
Hypersensitivity
Hemorrhage
Recovery
Injections

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. / Santagostino, Elena; Negrier, Claude; Klamroth, Robert; Tiede, Andreas; Pabinger-Fasching, Ingrid; Voigt, Christine; Jacobs, Iris; Morfini, Massimo.

In: Blood, Vol. 120, No. 12, 20.09.2012, p. 2405-2411.

Research output: Contribution to journalArticle

Santagostino, Elena ; Negrier, Claude ; Klamroth, Robert ; Tiede, Andreas ; Pabinger-Fasching, Ingrid ; Voigt, Christine ; Jacobs, Iris ; Morfini, Massimo. / Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. In: Blood. 2012 ; Vol. 120, No. 12. pp. 2405-2411.
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