Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A

T. E. Coyle, M. T. Reding, J. C. Lin, L. A. Michaels, A. Shah, Jerry S Powell

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Summary: Background: BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. Objectives: To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. Patients/Methods: This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21-58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg-1; cohort 2 [n = 7], 50 IU kg-1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg-1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg-1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. Results: BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. Conclusions: This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

Original languageEnglish (US)
Pages (from-to)488-496
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume12
Issue number4
DOIs
StatePublished - 2014

Keywords

  • Clinical trial, Phase 1
  • Factor VIII
  • Hemophilia A
  • Pharmacokinetics
  • Recombinant proteins

ASJC Scopus subject areas

  • Hematology

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