Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients

U. Martinowitz, T. Lissitchkov, A. Lubetsky, G. Jotov, T. Barazani-Brutman, C. Voigt, I. Jacobs, T. Wuerfel, E. Santagostino

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Introduction: rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. Aim: This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. Methods: The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Results: Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. Conclusion: This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalHaemophilia
Volume21
Issue number6
DOIs
Publication statusPublished - Nov 1 2015

Fingerprint

Recombinant Fusion Proteins
Hemophilia B
Factor IX
Albumins
Hemorrhage
Safety
Pharmacokinetics
Injections
Hemostatics
Therapeutics
Hemostasis
Half-Life

Keywords

  • Factor IX
  • Haemophilia B
  • Haemostasis
  • Pharmacokinetics
  • Prophylaxis

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients. / Martinowitz, U.; Lissitchkov, T.; Lubetsky, A.; Jotov, G.; Barazani-Brutman, T.; Voigt, C.; Jacobs, I.; Wuerfel, T.; Santagostino, E.

In: Haemophilia, Vol. 21, No. 6, 01.11.2015, p. 784-790.

Research output: Contribution to journalArticle

Martinowitz, U, Lissitchkov, T, Lubetsky, A, Jotov, G, Barazani-Brutman, T, Voigt, C, Jacobs, I, Wuerfel, T & Santagostino, E 2015, 'Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients', Haemophilia, vol. 21, no. 6, pp. 784-790. https://doi.org/10.1111/hae.12721
Martinowitz, U. ; Lissitchkov, T. ; Lubetsky, A. ; Jotov, G. ; Barazani-Brutman, T. ; Voigt, C. ; Jacobs, I. ; Wuerfel, T. ; Santagostino, E. / Results of a phase I/II open-label, safety and efficacy trial of coagulation factor IX (recombinant), albumin fusion protein in haemophilia B patients. In: Haemophilia. 2015 ; Vol. 21, No. 6. pp. 784-790.
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AU - Martinowitz, U.

AU - Lissitchkov, T.

AU - Lubetsky, A.

AU - Jotov, G.

AU - Barazani-Brutman, T.

AU - Voigt, C.

AU - Jacobs, I.

AU - Wuerfel, T.

AU - Santagostino, E.

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N2 - Introduction: rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. Aim: This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. Methods: The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Results: Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. Conclusion: This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.

AB - Introduction: rIX-FP is a coagulation factor IX (recombinant), albumin fusion protein with more than fivefold half-life prolongation over other standard factor IX (FIX) products available on the market. Aim: This prospective phase II, open-label study evaluated the safety and efficacy of rIX-FP for the prevention of bleeding episodes during weekly prophylaxis and assessed the haemostatic efficacy for on-demand treatment of bleeding episodes in previously treated patients with haemophilia B. Methods: The study consisted of a 10-14 day evaluation of rIX-FP pharmacokinetics (PK), and an 11 month safety and efficacy evaluation period with subjects receiving weekly prophylaxis treatment. Safety was evaluated by the occurrence of related adverse events, and immunogenic events, including development of inhibitors. Efficacy was evaluated by annualized spontaneous bleeding rate (AsBR), and the number of injections to achieve haemostasis. Results: Seventeen subjects participated in the study, 13 received weekly prophylaxis and 4 received episodic treatment only. No inhibitors were detected in any subject. The mean and median AsBR were 1.25, and 1.13 respectively in the weekly prophylaxis arm. All bleeding episodes were treated with 1 or 2 injections of rIX-FP. Three prophylaxis subjects who were treated on demand prior to study entry had >85% reduction in AsBR compared to the bleeding rate prior to study entry. Conclusion: This study demonstrated the efficacy for weekly routine prophylaxis of rIX-FP to prevent spontaneous bleeding episodes and for the treatment of bleeding episodes. In addition no safety issues were detected during the study and an improved PK profile was demonstrated.

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