A phase III clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in hemophilia patients with inhibitors: hemostatic efficacy and safety (WFH 2014) - May 3, 2014 - P3, N=21; Sponsor: rEVO Biologics; NCT02020369; "In 21 treatments for bleeding episodes, 19 were rated “excellent” or “effective” according to the investigator rating system 8 h after the last treatment. The VAS significantly decreased over time and the ROM significantly improved over time compared with the value before treatment. One mild adverse reaction and two serious adverse events were observed within one week after first administration with no significantly effect on safety."
P3 data • Hemophilia
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World Congress of Hemophilia, 11-15 May; Melbourne, Australia
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Introduction and Objectives: MC710, a 1:10 protein-weight-ratio mixture of plasmaderived activated factor VII (FVIIa) and factor X (FX) is a novel bypassing agent for hemostasis in hemophilia patients with inhibitors. MC710 administers FVIIa and its substrate FX concomitantly for greater potency than FVIIa alone, and is long-acting due to the long half-life of FX. We have already clarified dose-dependency of the pharmacokinetic/ pharmacodynamic parameters of MC710, and demonstrated hemostatic efficacy in a small number of joint bleedings in hemophilia patients with inhibitors. Moreover, we confirmed the safety of MC710 up to 120 lg/kg per dose (as FVIIa dose). We evaluated the hemostatic efficacy and safety of one to two administrations of MC710 in joint, muscle, and subcutaneous bleeding episodes of Japanese male hemophilia patients with inhibitors. Materials and Methods: This trial was a multicentre, open-label, non-randomized clinical study. All subjects provided written informed consent. Subjects were administered between one and two doses of 60 or 120 lg/kg MC710 (to a maximum of 180 lg/kg), intravenously, over up to five bleeding episodes per subject. Hemostatic efficacy of MC710 was determined for each episode by investigator evaluation using changes in visual analogue scale (VAS) for pain relief, and/or knee joint or muscle circumference for swelling reduction, and range of motion (ROM) for improvement of joint mobility. Results: In 21 treatments for bleeding episodes, 19 were rated “excellent” or “effective” according to the investigator rating system 8 h after the last treatment. The VAS significantly decreased over time and the ROM significantly improved over time compared with the value before treatment. One mild adverse reaction and two serious adverse events were observed within one week after first administration with no significantly effect on safety. In the subject administered twice with MC710, although D-dimer increased approximately two-fold 24 h after first administration compared to pre-treatment, platelet count and fibrinogen levels did not change. Subjects did not develop new viral antigens or produce new antibodies following MC710 administration. Conclusion: MC710 has sufficient hemostatic efficacy and safety, and can be used as a potential bypassing agent to control bleeding in hemophilia patients with inhibitors.
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