Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY Stroke Pub Date : 2024-11-07 DOI:10.1161/STROKEAHA.124.048464

Kuniyasu Niizuma, Naoko Nishimura, Keiko Hasegawa, Takashi Moritoyo, Kohsuke Kudo, Josh Bell, Michael Wald, Yoshifumi Umeda, Kazuhiko Kuribayashi, Yasuo Toda, Teiji Tominaga, Keiji Hasumi

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Abstract

Background: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a Stachybotrys microspora triprenyl phenol family member, may extend this therapeutic window.

Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2a study, JX10 or placebo was administered as a single intravenous infusion to Japanese patients with acute ischemic stroke who were unable to receive tissue-plasminogen activator or thrombectomy within 12 hours of last known normal. Primary end point was incidence of symptomatic intracranial hemorrhage with a worsening National Institutes of Health Stroke Scale score of ≥4 points within 24 hours of drug administration (symptomatic intracranial hemorrhage incidence).

Results: Ninety patients received either placebo (n=38; female 26.3%) or JX10 at 1, 3, or 6 mg/kg (n=6, 18, 28; female 0%, 33.3%, and 42.9%, respectively). Median age (range) and baseline median (range) National Institutes of Health Stroke Scale scores were respectively 76.5 (42-87) and 8 (6-21) for the combined JX10 cohort (JX10 Cohorts) and 75.0 (34-85) and 8 (6-22) for placebo. Median (range) dosing time since last known normal was 9.5 (5.0-12.1) and 10.0 (3.7-12.0) hours for JX10 Cohorts and placebo, respectively. Symptomatic intracranial hemorrhage incidence was 0% (0/52 [95% CI, 0.0-5.6]) for JX10 Cohorts versus 2.6% (1/38 [95% CI, 0.1-13.8]) for placebo (P=0.42). Vessel patency at 24 hours (secondary end point) in patients with baseline arterial occlusive lesion score <3 (39/90) improved in 58.3% (14/24) of patients in JX10 Cohorts versus 26.7% (4/15) for placebo (odds ratio, 4.23 [95% CI, 0.99-18.07]). In JX10 Cohorts, a significantly higher proportion of patients had modified Rankin Scale scores of 0 to 1 on day 90 (secondary end point) versus placebo (JX10: 21/52, 40.4% versus placebo: 7/38, 18.4%; P=0.03).

Conclusions: JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent.

Registration: URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.

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抗炎溶栓剂 JX10 (TMS-007) 在急性缺血性中风晚期表现中的应用

背景：目前治疗急性缺血性中风的溶栓药物仅限于在最后一次已知正常后 4.5 小时内使用。JX10（原名 TMS-007）是一种水苏糖三烯酚家族成员，可延长这一治疗时间：在这项多中心、随机、双盲、安慰剂对照、剂量递增的 2a 期研究中，JX10 或安慰剂以单次静脉输注的方式用于在最后一次已知正常后 12 小时内无法接受组织浆肌酶原激活剂或血栓切除术的急性缺血性脑卒中日本患者。主要终点是用药后24小时内症状性颅内出血发生率，且美国国立卫生研究院卒中量表评分恶化≥4分（症状性颅内出血发生率）：90名患者接受了安慰剂（n=38；女性占26.3%）或1、3或6毫克/千克的JX10（n=6、18、28；女性分别占0%、33.3%和42.9%）治疗。JX10联合队列（JX10队列）的中位数年龄（范围）和基线中位数（范围）美国国立卫生研究院卒中量表评分分别为76.5（42-87）和8（6-21），安慰剂的中位数年龄（范围）和基线中位数（范围）分别为75.0（34-85）和8（6-22）。JX10组群和安慰剂自最后一次已知正常后的用药时间中位数（范围）分别为9.5（5.0-12.1）小时和10.0（3.7-12.0）小时。JX10 Cohorts的症状性颅内出血发生率为0%（0/52 [95% CI, 0.0-5.6]），而安慰剂为2.6%（1/38 [95% CI, 0.1-13.8]）（P=0.42）。基线动脉闭塞病变评分患者 24 小时血管通畅率（次要终点）P=0.03）：JX10的耐受性良好，作为一种新型溶栓药物，它可能会扩大急性缺血性中风的治疗范围：URL：https://rctportal.niph.go.jp/en；唯一标识符：jRCT2080223786。

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来源期刊

Stroke 医学-临床神经学

CiteScore

13.40

自引率

6.00%

发文量

2021

审稿时长

3 months

期刊介绍： Stroke is a monthly publication that collates reports of clinical and basic investigation of any aspect of the cerebral circulation and its diseases. The publication covers a wide range of disciplines including anesthesiology, critical care medicine, epidemiology, internal medicine, neurology, neuro-ophthalmology, neuropathology, neuropsychology, neurosurgery, nuclear medicine, nursing, radiology, rehabilitation, speech pathology, vascular physiology, and vascular surgery. The audience of Stroke includes neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventionalists, neurosurgeons, nurses, and physiatrists. Stroke is indexed in Biological Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts, CINAHL, Current Contents, Embase, MEDLINE, and Science Citation Index Expanded.