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Multicenter Study
. 2012 Sep 20;120(12):2405-11.
doi: 10.1182/blood-2012-05-429688. Epub 2012 Aug 2.

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

Elena Santagostino  1 , Claude Negrier, Robert Klamroth, Andreas Tiede, Ingrid Pabinger-Fasching, Christine Voigt, Iris Jacobs, Massimo Morfini
Affiliations
Multicenter Study

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

Elena Santagostino et al. Blood. .

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 treatment-related 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.

Trial registration: ClinicalTrials.gov NCT01233440.

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Figures

Figure 1
Figure 1
Linear plot of baseline-corrected FIX activity level after the infusion of 50 IU/kg of rIX-FP and previous FIX product (PK population). Mean FIX activity levels of 50 IU/kg rIX-FP, 50 IU/kg rFIX, and 50 IU/kg pdFIX were measured in international units per decaliter. Vertical bars represent SD. A horizontal dotted line represents the 5-IU/dL FIX activity level.
Figure 2
Figure 2
Linear plot of baseline-corrected FIX activity level after infusion of 25, 50, or 75 IU/kg of rIX-FP (PK population). Mean FIX activity levels of 25, 50, and 75 IU/kg rIX-FP were measured in international units per decaliter. Vertical bars represent SD. A horizontal dotted line represents the 2-IU/dL and 5-IU/dL FIX activity levels.
See this image and copyright information in PMC

References

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