Results of clot waveform analysis and thrombin generation test for a plasma-derived factor VIIa and X mixture (MC710) in haemophilia patients with inhibitorsphase I trial: 2nd report

被引：18

作者：

Shirahata, A. ^{[1
]}

Fukutake, K. ^{[2
]}

Mimaya, J. ^{[3
]}

Takamatsu, J. ^{[4
]}

Shima, M. ^{[5
]}

Hanabusa, H. ^{[6
]}

Takedani, H. ^{[7
]}

Takashima, Y. ^{[2
]}

Matsushita, T. ^{[8
]}

Tawa, A. ^{[9
]}

Higasa, S. ^{[10
]}

Takata, N. ^{[11
]}

Sakai, M. ^{[1
]}

Kawakami, K. ^{[12
]}

Ohashi, Y. ^{[13
]}

Saito, H. ^{[14
]}

机构：

[1] Univ Occupat & Environm Hlth, Dept Paediat, Kitakyushu, Fukuoka 807, Japan

[2] Tokyo Med Univ, Dept Lab Med, Tokyo 1608402, Japan

[3] Shizuoka Childrens Hosp, Div Haematol & Oncol, Shizuoka, Japan

[4] Nagoya Univ Hosp, Dept Transfus Med, Nagoya, Aichi, Japan

[5] Nara Med Univ, Dept Paediat, Kashihara, Nara 634, Japan

[6] Ogikubo Hosp, Dept Haematol, Tokyo, Japan

[7] Univ Tokyo, Inst Med Sci, Res Hosp, Dept Joint Surg, Tokyo, Japan

[8] Nagoya Univ, Grad Sch Med, Dept Haematol & Oncol, Nagoya, Aichi 4648601, Japan

[9] Natl Hosp Org Osaka Natl Hosp, Dept Paediat, Osaka, Japan

[10] Hyogo Coll Med, Dept Internal Med, Div Haematol, Nishinomiya, Hyogo 6638501, Japan

[11] Hiroshima Univ Hosp, Div Blood Transfus Serv, Hiroshima, Japan

[12] Kagoshima City Hosp, Dept Paediat, Kagoshima, Japan

[13] Univ Tokyo, Sch Publ Hlth, Dept Biostat, Tokyo, Japan

[14] Nagoya Cent Hosp, Nagoya, Aichi, Japan

来源：

HAEMOPHILIA | 2013年 / 19卷 / 02期

关键词：

bypassing agent; clot waveform analysis; factor VIIa; factor X; haemophiliacs with inhibitors; thrombin generation test; DISSEMINATED INTRAVASCULAR COAGULATION; ACTIVATED FACTOR-VII; HIGH-DOSE FACTOR; TISSUE FACTOR; COMPLEX; MODEL;

D O I：

10.1111/hae.12024

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We reported the results of a clinical pharmacological study of MC710 (a mixture of plasma-derived FVIIa and FX) in haemophilia patients with inhibitors during a non-haemorrhagic state. This report provides the results of a clot waveform analysis (CWA) and thrombin generation test (TGT) using blood samples obtained in this study. CWA and TGT were conducted using blood samples obtained from a pharmacokinetic and pharmacodynamic study in which MC710 (five dose rates: 20, 40, 80, 100 and 120gkg1) was compared with NovoSeven (120gkg1) and FEIBA (two dose rates: 50 and 75Ukg1) as control drugs in 11 haemophilia patients with inhibitors without haemorrhagic symptoms. CWA showed that MC710 provided significantly greater improvement than the control drugs in activated partial thromboplastin time (APTT) at 80gkg1; maximum clot velocity and maximum clot acceleration were more enhanced by MC710 than by control drugs. TGT revealed that MC710 significantly shortened the initiation time of thrombin generation in comparison to FEIBA and induced greater thrombin generation potency than NovoSeven. It was not clear whether or not MC710 caused significant dose-dependent changes in the two measurements; however, differences between MC710 and the control drugs were clarified. MC710 was confirmed to have superior coagulation activity and thrombin productivity and is expected to have superior bypassing activity.

引用

页码：330 / 337

页数：8

共 7 条

[1] Clinical pharmacological study of a plasma-derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors - Phase I trial
Shirahata, A.
Fukutake, K.
Mimaya, J.
Takamatsu, J.
Shima, M.
Hanabusa, H.
Takedani, H.
Takashima, Y.
Matsushita, T.
Tawa, A.
Higasa, S.
Takata, N.
Sakai, M.
Kawakami, K.
Ohashi, Y.
Saito, H.
HAEMOPHILIA, 2012, 18 (01) : 94 - 101
[2] Clinical pharmacological study of a plasma-derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors - phase I trial
Matsushita, T.
Shirahata, A.
Fukutake, K.
Mimaya, J.
Takamatsu, J.
Shima, M.
Hanabusa, H.
Takedani, H.
Takashima, Y.
Tawa, A.
Higasa, S.
Takata, N.
Sakai, M.
Kawakami, K.
Ohashi, Y.
Saito, H.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 : 513 - 513
[3] Plasma-derived factor VIIa and factor X mixture agent (MC710) prophylaxis in haemophilia B patients with inhibitors
Sakai, Michio
Amano, Kagehiro
Chin, Motoaki
Takedani, Hideyuki
Ishida, Hiroyuki
Sakashita, Kazuo
Taki, Masashi
Migita, Masahiro
Watanabe, Hiroyoshi
Ishimura, Masataka
Nogami, Keiji
Harano, Sho
Shirahata, Akira
HAEMOPHILIA, 2023, 29 (02) : 456 - 465
[4] A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors
Shinkoda, Y.
Shirahata, A.
Fukutake, K.
Takamatsu, J.
Shima, M.
Hanabusa, H.
Mugishima, H.
Takedani, H.
Kawasugi, K.
Taki, M.
Matsushita, T.
Tawa, A.
Nogami, K.
Higasa, S.
Kosaka, Y.
Fujii, T.
Sakai, M.
Migita, M.
Uchiba, M.
Kawakami, K.
Sameshima, K.
Ohashi, Y.
Saito, H.
HAEMOPHILIA, 2017, 23 (01) : 59 - 66
[5] A Phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics
Shirahata, A.
Fukutake, K.
Takamatsu, J.
Shima, M.
Hanabusa, H.
Mugishima, H.
Amano, K.
Takedani, H.
Tamashima, S.
Matsushita, T.
Tawa, A.
Tanaka, I.
Higasa, S.
Kosaka, Y.
Fujii, T.
Sakai, M.
Migita, M.
Kawakami, K.
Ohashi, Y.
Saito, H.
HAEMOPHILIA, 2013, 19 (06) : 853 - 860
[6] Results of haemostatic efficacy, safety, and pharmacokinetics/pharmacodynamics of a plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: phase II clinical trial
Amano, K.
Shirahata, A.
Fukutake, K.
Takamatsu, J.
Shima, M.
Higasa, S.
Fujii, T.
Migita, M.
Kawakami, K.
Saito, H.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2013, 11 : 170 - 171
[7] 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
Shinkoda, Yuichi
Sameshima, Koji
Fukutake, Katsuyuki
Takamatsu, Junki
Shima, Midori
Shirahata, Akira
Saito, Hidehiko
HAEMOPHILIA, 2014, 20 : 43 - 43

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