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Efficacy and safety of rVIII-SingleChain: Results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Mahlangu, J., Kuliczkowski, K., Karim, F.A., Stasyshyn, O., Kosinova, M.V., Lepatan, L.M., Skotnicki, A., Boggio, L.N., Klamroth, R., Oldenburg, J., Hellmann, A., Santagostino, E., Baker, R.I., Fischer, K., Gill, J.C., Ng, S.P., Chowdary, P., Escobar, M.A., Khayat, C.D., Rusen, L., Bensen-Kennedy, D., Blackman, N., Limsakun, T., Veldman, A., St. Ledger, K. and Pabinger, I. (2016) Efficacy and safety of rVIII-SingleChain: Results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood, 128 (5). pp. 630-637.

Link to Published Version: http://dx.doi.org/10.1182/blood-2016-01-687434
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Abstract

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

Publication Type: Journal Article
Murdoch Affiliation: Centre for Haemophilia and Thrombosis Research
Publisher: American Society of Hematology
Copyright: © 2016 by The American Society of Hematology
URI: http://researchrepository.murdoch.edu.au/id/eprint/32717
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