title: A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors.
abstract: BACKGROUND
  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-1MC710 (as FVIIa) once or twice (to a maximum of 180 μg kg-1) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shinkoda
authors.affiliation: Kitakyushu Yahata Higashi Hospital, Kitakyushu, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shirahata
authors.affiliation: Department of Laboratory Medicine, Tokyo Medical University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukutake
authors.affiliation: Japanese Red Cross Tokai-Hokuriku Block Blood Center, Seto, Aichi, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Takamatsu
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shima
authors.affiliation: Department of Haematology, Ogikubo Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Department of Paediatrics, Nihon University Itabashi Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mugishima
authors.affiliation: Department of Joint Surgery, Research Hospital of the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takedani
authors.affiliation: Department of Internal Medicine, Teikyo University Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawasugi
authors.affiliation: Department of Paediatrics, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Taki
authors.affiliation: Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Paediatrics, National Hospital Organization Osaka National Hospital, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Department of Paediatrics, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nogami
authors.affiliation: Division of Haematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Higasa
authors.affiliation: Department of Haematology and Oncology, Kobe Children's Hospital, Kobe, Hyogo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Division of Blood Transfusion, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Paediatrics, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Department of Paediatrics, Kumamoto Red Cross Hospital, Kumamoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Migita
authors.affiliation: Department of Blood Transfusion and Cell Therapy, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Uchiba
authors.affiliation: Department of Paediatrics, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Paediatrics, Kagoshima City Hospital, Kagoshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sameshima
authors.affiliation: Department of Biostatistics, School of Public Health, the University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000293:Adolescent; D000328:Adult; D015942:Factor VIIa / Q000627:therapeutic use*; D005170:Factor X / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D005170:Factor X; D015942:Factor VIIa
keywords: FX; activated FVII; bypassing agents; haemophilia patient with inhibitors; haemostatic efficacy; safety