Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A

Johnny Mahlangu, Jerry S Powell, Margaret V. Ragni, Pratima Chowdary, Neil C. Josephson, Ingrid Pabinger, Hideji Hanabusa, Naresh Gupta, Roshni Kulkarni, Patrick Fogarty, David Perry, Amy Shapiro, K. John Pasi, Shashikant Apte, Ivan Nestorov, Haiyan Jiang, Shuanglian Li, Srividya Neelakantan, Lynda M. Cristiano, Jaya GoyalJurg M. Sommer, Jennifer A. Dumont, Nigel Dodd, Karen Nugent, Gloria Vigliani, Alvin Luk, Aoife Brennan, Glenn F. Pierce

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235 Scopus citations

Abstract

This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). a subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-foldvsrFVIII (12.4 hours; P <.001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week. This trial was registered at www.clinicaltrials.gov as #NCT01181128.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalBlood
Volume123
Issue number3
DOIs
StatePublished - Jan 16 2014

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Mahlangu, J., Powell, J. S., Ragni, M. V., Chowdary, P., Josephson, N. C., Pabinger, I., Hanabusa, H., Gupta, N., Kulkarni, R., Fogarty, P., Perry, D., Shapiro, A., Pasi, K. J., Apte, S., Nestorov, I., Jiang, H., Li, S., Neelakantan, S., Cristiano, L. M., ... Pierce, G. F. (2014). Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 123(3), 317-325. https://doi.org/10.1182/blood-2013-10-529974