{"title":"抗炎溶栓剂 JX10 (TMS-007) 在急性缺血性中风晚期表现中的应用","authors":"Kuniyasu Niizuma, Naoko Nishimura, Keiko Hasegawa, Takashi Moritoyo, Kohsuke Kudo, Josh Bell, Michael Wald, Yoshifumi Umeda, Kazuhiko Kuribayashi, Yasuo Toda, Teiji Tominaga, Keiji Hasumi","doi":"10.1161/STROKEAHA.124.048464","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a <i>Stachybotrys microspora</i> triprenyl phenol family member, may extend this therapeutic window.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 (<i>P</i>=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%; <i>P</i>=0.03).</p><p><strong>Conclusions: </strong>JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent.</p><p><strong>Registration: </strong>URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.\",\"authors\":\"Kuniyasu Niizuma, Naoko Nishimura, Keiko Hasegawa, Takashi Moritoyo, Kohsuke Kudo, Josh Bell, Michael Wald, Yoshifumi Umeda, Kazuhiko Kuribayashi, Yasuo Toda, Teiji Tominaga, Keiji Hasumi\",\"doi\":\"10.1161/STROKEAHA.124.048464\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a <i>Stachybotrys microspora</i> triprenyl phenol family member, may extend this therapeutic window.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 (<i>P</i>=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%; <i>P</i>=0.03).</p><p><strong>Conclusions: </strong>JX10 was well tolerated and may expand the acute ischemic stroke therapeutic window as a novel thrombolytic agent.</p><p><strong>Registration: </strong>URL: https://rctportal.niph.go.jp/en; Unique identifier: jRCT2080223786.</p>\",\"PeriodicalId\":21989,\"journal\":{\"name\":\"Stroke\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2024-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/STROKEAHA.124.048464\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/STROKEAHA.124.048464","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.
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.
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.
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