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

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-1 MC710 (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). 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.

Twenty-five types of T-cell receptor Vbeta family repertoire in patients with Kawasaki syndrome.

UNLABELLED: Recently, a possible relationship between Kawasaki syndrome (KS) and superantigen has been discussed since the report of selective expansion of specific Vbeta family in the acute phase of KS. To further investigate the relationship between KS and superantigens, we examined 25 types of T-cell receptor Vbeta family repertoire in patients with KS using the reverse transcription polymerase chain reaction. This is the first attempt to examine all of 25 Vbeta families in KS. A non radioisotope method was used to quantify mRNA so that the experiment was safer, simpler, and faster. An expression index (EI) for each Vbeta was defined as: (the amount of each Vbeta mRNA)/(the sum of all Vbeta mRNA) x 100. Ten patients with KS and ten normal children were studied. The Vbeta9 and Vbeta15 of acute phase of KS showed both significantly lower mean EI and significantly higher frequency of a decreased EI value as compared with control children. Selective expansion of the Vbeta family in the patients with KS was not observed. Although highly increased EIs were observed in various Vbetas, their frequency was not statistically significant. The pattern of increased Vbetas did not show the specific pattern that indicates a particular superantigen. CONCLUSION: In Kawasaki syndrome non-radioisotope method for analysing Vbeta mRNA is useful in cases where many samples have to be handled. The depletion of Vbeta9 and Vbeta15 or highly increased expression index in the acute phase of Kawasaki syndrome might suggest a relationship to superantigens.