曲纤溶酶原α(Troplasminogen alfa) - 药物靶点：PLG_专利_临床

概要

基本信息

药物类型

酶

别名

Tapgen

+ [4]

靶点

PLG

作用机制

PLG刺激剂(纤溶酶原刺激剂)

治疗领域

神经系统疾病心血管疾病

在研适应症-

非在研适应症

急性缺血性卒中脑卒中血栓形成

原研机构

Ligand UK Ltd.

在研机构-

非在研机构

Vernalis (R&D) Ltd.

BTG International Ltd.

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 546437760

来源: *****

关联

3

项与曲纤溶酶原α 相关的临床试验

EUCTR2007-007643-27-CZ / Not yet recruitingN/A

A Phase IIa, Multi-Centre Study to Evaluate the Safety and Efficacy of V10153 in Acute Ischaemic Stroke - VASTT

开始日期2008-05-21

申办/合作机构-

EUCTR2007-007643-27-DK / Not yet recruitingN/A

A Phase IIa, Multi-Centre Study to Evaluate the Safety and Efficacy of V10153 in Acute Ischaemic Stroke - VASTT

开始日期2008-03-28

申办/合作机构-

NCT00144014 / Completed临床2期

A Phase II, Multi-centre, Two-part Study to Evaluate the Safety and Efficacy of Study Drug in Acute Ischaemic Stroke.

A Phase II study to evaluate the safety and efficacy of five dose levels of study drug in acute ischaemic stroke

开始日期2005-08-01

申办/合作机构

Vernalis (R&D) Ltd.

100 项与曲纤溶酶原α 相关的临床结果

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100 项与曲纤溶酶原α 相关的转化医学

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100 项与曲纤溶酶原α 相关的专利（医药）

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5

项与曲纤溶酶原α 相关的文献（医药）

2006-08-01·Journal of Thrombosis and Thrombolysis4区 · 医学

Dose escalation trial of the efficacy, safety, and pharmacokinetics of a novel fibrinolytic agent, BB-10153, in patients with ST elevation MI: Results of the TIMI 31 trial

4区 · 医学

Article

作者: Cafer Zorkun ; Hans Louwerenburg ; Sabina A. Murphy ; Krzysztof Zmudka ; Mahesh Bikkina ; Hiltrud Mueller ; Jaap Westenburg ; Mark Greenberg ; John Batty ; Jobst De Winter ; Alan Niederman ; Jan Wesdorp ; Carolyn H. Mccabe ; C. Michael Gibson ; Peter Molhoek

BACKGROUNDCurrently available fibrinolytic agents are limited by their ability to restore normal blood flow in only half of patients, the risk of reocclusion, and the risk of intracranial hemorrhage. The genetically engineered agent BB-10153 is activated by thrombin, not plasminogen activator enzymes, which limits its activity to the site of thrombus which may in turn reduce the risk of systemic bleeding. BB-10153 also has a relatively long half-life of 3-4 hours, which may also limit the potential for early reocclusion [1, 2].METHODSThe study was a phase II, open-label, multi-center, dose escalation, single-dose administration study to determine the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of BB-10153 in ST segment elevation MI (STEMI). STEMI patients (n = 50) received a single dose of BB-10153 at one of six dose levels (1.0, 2.0, 3.0, 5.0, 7.5 and 10 mg/kg). The primary endpoint was TIMI flow grade (TFG) 3 at 60 minutes following the intravenous bolus of BB-10153.RESULTSMean area under the curve for drug concentration ranged from 48.0 microg.h/mL in the 1 mg/kg dose group to 788.6 microg.h/mL in the 10 mg/kg dose group. Likewise, mean Cmax generally increased with dose over the entire dose range, from 4.9 microg/mL in the 1 mg/kg dose group to 139.6 microg/mL in the 10 mg/kg dose group. The mean apparent terminal half-life (t1/2) was 4.4 hours (range 2.2 to 7.6 hours). Few patients in the 1-3 mg/kg dosage groups achieved TFG 3 on the one-hour post-dose angiogram (4/20, 20%), and no patients achieved complete ST segment resolution. The 5, 7.5 and 10 mg/kg doses were associated with similar rates of TIMI grade 3 flow of approximately three per seven patients. Pooling TFG 3 data from the 5, 7.5 and 10 mg/kg groups yielded a TIMI grade 3 flow rate of 34% (n = 10/29; range 29-43%). No patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. One patient experienced recurrent angina and developed recurrent myocardial ischemia requiring urgent revascularization. Three patients sustained TIMI major bleeding events (one in 1 mg/kg group, two in 7.5 mg/kg group), six patients sustained TIMI minor bleeds (one in the 2, 3, 7.5 and 10 mg/kg groups, two in the 5 mg/kg group), twp patients sustained TIMI minimal bleeds (one in each of the 2 and 10 mg/kg groups) and no patients sustained intracranial hemorrhage (ICH).CONCLUSIONIn a dose escalation study of a single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the mean area under the curve and Cmax for drug concentration over the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study. In a dose escalation study of a single intravenous bolus, the novel fibrinolytic agent, BB-10153 was associated with a rise in the mean area under the curve and Cmax for drug concentration over the dose range 1 to 10 mg/kg. Higher doses were associated with a range of TIMI grade 3 flow of 29-43%, and no patients experienced 30-day death, recurrent acute MI, cardiogenic shock, stroke or anaphylaxis during the study.

2005-09-01·Current opinion in investigational drugs (London, England : 2000)

V-10153 (Vernalis).

Article

作者: Kamali, Farhad

Vernalis is developing V-10153, a recombinant plasminogen activator stimulator, for the potential treatment of thrombotic disorders and cardiovascular disease. By March 2004, a phase II trial in acute myocardial infarction had been completed, and by July 2005, Vernalis intended to initiate a phase II trial in stroke later that same year.

2005-06-01·Journal of Thrombosis and Haemostasis2区 · 医学

Pharmacokinetics and pharmacodynamics of BB‐10153 , a thrombin‐activatable plasminogen, in healthy volunteers

2区 · 医学

Article

作者: P.L. Meroni ; M. Cugno ; L. Gregorini ; J. Nussberger ; F. Donatelli ; P. Agostoni ; G.B. Anguissola ; D. Mari ; M. Bussotti

BACKGROUNDBB-10153 is an engineered variant of human plasminogen that is activated to plasmin by thrombin. Thrombus-selective induction of reperfusion and prevention of reocclusion have been demonstrated following bolus administration in animal models of thrombosis.OBJECTIVE AND METHODSThe objective of the study was to examine the pharmacokinetics and pharmacodynamics of BB-10153 administered as an intravenous bolus to healthy male human volunteers. Cohorts of four were dosed with BB-10153 (n = 3) or placebo (n = 1). In total, placebo was received by eight volunteers and 0.08, 0.2, 0.6, 1.2, 1.8, 2.4, 3.6 and 4.8 mg kg(-1) BB-10153 by three volunteers each.RESULTSThere was a linear relationship between AUC/Cmax and dose. The half-life of BB-10153 was approximately 3-4 h and all the BB-10153 in the circulation retained the ability to be activated by thrombin. There was a dose-related increase in plasma fibrin D-dimers. Ex vivo plasma clot lysis was observed at doses of 3.6 and 4.8 mg kg(-1), whereas lysis of clots formed from euglobulin-fractionated plasma was first evident at 0.6 mg kg(-1) and activity increased with dose. This activity decreased with time in line with the half-life. BB-10153 had no effect on plasma alpha2-antiplasmin or fibrinogen levels, coagulation assays or bleeding time. An increase in plasminogen was observed as BB-10153 was detected by the enzyme-linked immunosorbent assay (ELISA) for human plasminogen.CONCLUSIONSBB-10153 was well tolerated and had a 3-4-h plasma half-life. Fibrinolytic activity was demonstrated by dose-related ex vivo clot lysis and in vivo production of fibrin D-dimers. These effects were not accompanied by consumption of alpha2-antiplasmin or fibrinogen.

100 项与曲纤溶酶原α 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑卒中	临床2期	丹麦	Vernalis (R&D) Ltd.	2008-03-28
脑卒中	临床2期	匈牙利	Vernalis (R&D) Ltd.	2008-03-28
脑卒中	临床2期	捷克	Vernalis (R&D) Ltd.	2008-03-28
急性缺血性卒中	临床2期	加拿大	Vernalis (R&D) Ltd.	2005-08-01
急性缺血性卒中	临床2期	美国	Vernalis (R&D) Ltd.	2005-08-01
血栓形成	临床2期	英国	BTG International Ltd.	2005-01-01