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

Johnny Mahlangu, Kazimierz Kuliczkowski, Faraizah Abdul Karim, Oleksandra Stasyshyn, Marina V. Kosinova, Lynda Mae Lepatan, Aleksander Skotnicki, Lisa N. Boggio, Robert Klamroth, Johannes Oldenburg, Andrzej Hellmann, Elena Santagostino, Ross I. Baker, Kathelijn Fischer, Joan C. Gill, Stephanie P'Ng, Pratima Chowdary, Miguel A. Escobar, Claudia Djambas Khayat, Luminita RusenDebra Bensen-Kennedy, Nicole Blackman, Tharin Limsakun, Alex Veldman, Katie St Ledger, Ingrid Pabinger

Research output: Contribution to journalArticle

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 5 146) or on-demand (N 5 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.

Original languageEnglish
Pages (from-to)630-637
Number of pages8
JournalBlood
Volume128
Issue number5
DOIs
Publication statusPublished - Aug 4 2016

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Medicine(all)
  • Hematology
  • Cell Biology

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    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., P'Ng, S., Chowdary, P., Escobar, M. A., Khayat, C. D., ... 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), 630-637. https://doi.org/10.1182/blood-2016-01-687434