Journal article
Efficacy and safety of rVIII-SingleChain: Results of a phase 1/3 multicenter clinical trial in severe hemophilia A
Blood, Vol.128(5), pp.630-637
2016
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.
Details
- Title
- Efficacy and safety of rVIII-SingleChain: Results of a phase 1/3 multicenter clinical trial in severe hemophilia A
- Authors/Creators
- J. Mahlangu (Author/Creator)K. Kuliczkowski (Author/Creator)F.A. Karim (Author/Creator)O. Stasyshyn (Author/Creator)M.V. Kosinova (Author/Creator)L.M. Lepatan (Author/Creator)A. Skotnicki (Author/Creator)L.N. Boggio (Author/Creator)R. Klamroth (Author/Creator)J. Oldenburg (Author/Creator)A. Hellmann (Author/Creator)E. Santagostino (Author/Creator)R.I. Baker (Author/Creator)K. Fischer (Author/Creator)J.C. Gill (Author/Creator)S.P. Ng (Author/Creator)P. Chowdary (Author/Creator)M.A. Escobar (Author/Creator)C.D. Khayat (Author/Creator)L. Rusen (Author/Creator)D. Bensen-Kennedy (Author/Creator)N. Blackman (Author/Creator)T. Limsakun (Author/Creator)A. Veldman (Author/Creator)K. St. Ledger (Author/Creator)I. Pabinger (Author/Creator)
- Publication Details
- Blood, Vol.128(5), pp.630-637
- Publisher
- American Society of Hematology
- Identifiers
- 991005543886807891
- Copyright
- © 2016 by The American Society of Hematology
- Murdoch Affiliation
- Centre for Haemophilia and Thrombosis Research
- Language
- English
- Resource Type
- Journal article
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- 1.75 Blood Clotting
- 1.75.619 Bleeding Disorders
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- Clinical Medicine