A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors.

Y Shinkoda, A Shirahata, K Fukutake, J Takamatsu, M Shima, H Hanabusa, H Mugishima, H Takedani, K Kawasugi, M Taki, T Matsushita, A Tawa, K Nogami, S Higasa, Y Kosaka, T Fujii, M Sakai, M Migita, M Uchiba, K Kawakami, K Sameshima, Y Ohashi, H Saito

Journal: Haemophilia : the official journal of the World Federation of Hemophilia 2017;23(1):59-66

PMID: 27480904

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Abstract

INTRODUCTION

MC710, a 1:10 protein weight ratio mixture of plasma-derived activated factor VII (FVIIa) and factor X (FX), is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. We evaluated the haemostatic efficacy and safety of one to two administrations of MC710 in 21 joint, muscle, and subcutaneous bleeding episodes in 14 male patients, in a multi-centre, open-label, non-randomized clinical trial.

METHODS

Subjects were intravenously administered one or two doses of 60 or 120 μg kg MC710 (as FVIIa) once or twice (to a maximum of 180 μg kg ) over up to five bleeding episodes per subject. The haemostatic 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" 8 h after the last treatment. VAS significantly decreased over time, and ROM significantly improved over time compared with the values before treatment. One mild adverse reaction, decreased blood potassium, and two serious adverse events, both knee joint bleeding, were observed within 1 week after first administration, with no significant effect on safety. Furthermore, diagnostic markers did not show any signs of disseminated intravascular coagulation (DIC).

CONCLUSION

These results show that MC710 has sufficient haemostatic efficacy and safety, and can be used as a potential bypassing agent to control bleeding in haemophilia patients with inhibitors.

Address: Department of Paediatrics, Kagoshima City Hospital, Kagoshima, Japan.; Kitakyushu Yahata Higashi Hospital, Kitakyushu, Fukuoka, Japan.; Department of Laboratory Medicine, Tokyo Medical University, Tokyo, Japan.; Japanese Red Cross Tokai-Hokuriku Block Blood Center, Seto, Aichi, Japan.; Department of Paediatrics, Nara Medical University, Kashihara, Nara, Japan.; Department of Haematology, Ogikubo Hospital, Tokyo, Japan.; Department of Paediatrics, Nihon University Itabashi Hospital, Tokyo, Japan.; Department of Joint Surgery, Research Hospital of the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.; Department of Internal Medicine, Teikyo University Hospital, Tokyo, Japan.; Department of Paediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.; Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Aichi, Japan.; Department of Paediatrics, National Hospital Organization Osaka National Hospital, Osaka, Japan.; Division of Haematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.; Department of Haematology and Oncology, Kobe Children's Hospital, Kobe, Hyogo, Japan.; Division of Blood Transfusion, Hiroshima University Hospital, Hiroshima, Japan.; Department of Paediatrics, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.; Department of Paediatrics, Kumamoto Red Cross Hospital, Kumamoto, Japan.; Department of Blood Transfusion and Cell Therapy, Kumamoto University Hospital, Kumamoto, Japan.; Department of Biostatistics, School of Public Health, the University of Tokyo, Tokyo, Japan.; National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.

DOI: 10.1111/hae.13050

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MeSH Terms: Adolescent, Adult, Factor VIIa, Factor X, Hemophilia A, Humans, Male, Young Adult