Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children: Results of a phase 3 trial

Gili Kenet, Hervé Chambost, Christoph Male, Thierry Lambert, Susan Halimeh, Tatiana Chernova, Mariaelisa Mancuso, Julie Curtin, Christine Voigt, Yanyan Li, Iris Jacobs, Elena Santagostino, Maria Teresa Álvarez-Roman, Anthony Chan, Christopher Barnes, Jan Blatny, Sandrine Meunier, Vladimir Komrska, Hans Juergen Laws, Massimo MorfiniBohumir Blazek, PROLONG-9FP Investigator Study Group

Research output: Contribution to journalArticle

Abstract

A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531).

Original languageEnglish
Pages (from-to)659-668
Number of pages10
JournalThrombosis and Haemostasis
Volume116
Issue number4
DOIs
Publication statusPublished - Oct 1 2016

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Keywords

  • Factor IX
  • Haemophilia B
  • On-demand treatment
  • Prophylactic regimen
  • RIX-FP

ASJC Scopus subject areas

  • Hematology

Cite this

Kenet, G., Chambost, H., Male, C., Lambert, T., Halimeh, S., Chernova, T., Mancuso, M., Curtin, J., Voigt, C., Li, Y., Jacobs, I., Santagostino, E., Álvarez-Roman, M. T., Chan, A., Barnes, C., Blatny, J., Meunier, S., Komrska, V., Laws, H. J., ... PROLONG-9FP Investigator Study Group (2016). Long-acting recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in children: Results of a phase 3 trial. Thrombosis and Haemostasis, 116(4), 659-668. https://doi.org/10.1160/TH16-03-0179