A Phase II, Randomized, Placebo-Controlled, Double-Blind, Adaptive Study to Assess the Safety and Efficacy of Intravenous J147 Combined With Endovascular Therapy in Patients With Acute Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 196
- 试验地点
- 6
- 主要终点
- Safety of J147 Emulsion for Injection (J147) when administered with endovascular therapy in acute ischemic stroke patients.
研究概览
简要总结
The goal of this clinical trial is to find out if the drug J147 improves outcomes for persons who have had an ischemic stroke. It also will learn about the safety of J147 when given by injection to stroke patients. Researchers will compare the outcomes of those who receive J147 after therapy to clear the blood clot to those who don't receive J147. Participants will be asked to undergo a series of three to four magnetic resonance imaging (MRI) brain scans, and blood samples will be collected at several time points. Participants will also be evaluated to measure several aspects of brain function.
详细描述
This is a prospective, multicenter, double-blind, randomized, placebo-controlled, adaptive Phase II clinical study to evaluate the administration of J147 Emulsion for Injection (J147) in patients with acute ischemic stroke (AIS) with confirmed large vessel occlusion who undergo mechanical thrombectomy without intravenous thrombolytic therapy (alteplase or tenecteplase) and are candidates for reperfusion therapies.
Participants will undergo mechanical thrombectomy per standard of care. Following confirmation of successful reperfusion, eligible participants will receive a single intravenous bolus injection of blinded J147 Emulsion for Injection or placebo.
The study will be conducted in two sequential cohorts. In the first cohort, two dose levels of J147 will be evaluated in comparison with placebo. Based on an interim safety and efficacy review conducted by an independent Data Safety Monitoring Board (DSMB), a target dose will be selected for evaluation in the second cohort. Participants in the second cohort will be randomized to receive the selected dose of J147 or placebo.
The objective of the study is to evaluate the safety and tolerability of J147 at different dose levels compared with placebo when administered in combination with mechanical thrombectomy without intravenous thrombolytic therapy, and to explore its potential effects on imaging, biological, and clinical outcomes in the AIS target population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent obtained from the patient or legally authorized representative.
- •A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
- •Baseline NIHSS ≥5 and ≤25 points obtained prior to randomization with a disabling neurological deficit as determined by clinical judgement.
- •Pre-stroke mRS score of 0-
- •Availability to be treated within 24 hours of last known well.
- •Candidates to receive EVT treatment without IV thrombolytic therapy. Such patients should be initiated as recommended by the local standard of care for the early management of patients with AIS.
- •eTICI or better reperfusion achieved after completion of EVT.
- •Females, unless they are permanently sterile (e.g., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal (defined as no menses for at least 12 consecutive months without an alternative medical cause and, when applicable, confirmed by serum follicle stimulating hormone [FSH] level) must agree to use highly effective methods of contraception during the study and for a minimum of 30 days after the last dose of study drug. In women aged <45 years who report being postmenopausal, postmenopausal status must be confirmed by a serum FSH level in the postmenopausal range according to the laboratory's reference values. Until postmenopausal status is confirmed, these participants must remain abstinent or use a highly effective method of contraception. Highly effective methods include:
- •Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal, or injectable).
- •Progestogen-only hormonal contraception (oral, injectable, or implantable).
- •Intrauterine device (IUD).
- •Intrauterine hormone-releasing system (IUS).
- •Bilateral tubal occlusion.
- •Sexual abstinence, if consistent with the participant's usual lifestyle.
- •Vasectomized partner, provided the partner is the sole sexual partner and the vasectomy has been confirmed with a negative sperm count.
- •Barrier methods (e.g., condoms with spermicide, diaphragms) are not considered highly effective and should only be used as additional protection.
- •Women of childbearing potential (WOCBP) must have a negative urine pregnancy test before enrollment.
- •Male participants with WOCBP partners must either:
- •Be vasectomized, or
- •Agree to use condoms with spermicide plus an additional highly effective method of contraception used by the female partner, during the study and for 30 days after the last dose of study drug.
- •Men must also agree not to donate sperm during the study and for the same period post-treatment.
- •Specific Neuroimaging Inclusion Criteria
- •Occlusion of an internal carotid, middle cerebral, anterior cerebral, posterior cerebral artery, suitable for mechanical embolectomy, confirmed on vascular imaging. Tandem extra-intracranial lesions may be included.
- •The following imaging criteria should also be met on admission neuroimaging:
- •MRI criterion: volume of DWI ≥5 and ≤70 mL determined by any validated, automated artificial intelligence (AI) thresholding estimates of core and penumbra for participant selection and mismatch volume at least 25 mL, mismatch ratio at least 1.8 and a hypoperfusion intensity ratio 0.4 or higher.
排除标准
- •Absolute contraindication to MRI with gadolinium contrast.
- •Serious, advanced, or terminal illness with an anticipated life expectancy of <6 months.
- •History of life-threatening allergy (more than rash) to contrast medium.
- •Known renal insufficiency with creatinine ≥3 mg/dL or glomerular filtration rate (GFR) of <30 mL/min.
- •Clinically significant hepatic impairment, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper level of normal (ULN) and/or total bilirubin >1.5× ULN, unless attributable to a known diagnosis of Gilbert's syndrome without other evidence of liver dysfunction.
- •Patients that have received intravenous or intra-arterial thrombolytic for the current stroke prior to mechanical thrombectomy.
- •Patients participating in a study involving an investigational drug or device.
- •Any clinically significant medical history, physical examination finding, laboratory abnormality, vital sign abnormality, or 12-Lead ECG finding that, in the opinion of the investigator, may pose a risk to the patient's safety or well-being, interfere with the patient's ability to participate fully in the study, or confound the interpretation of study results.
- •Patients that are unlikely to be available for a 90-day follow up.
- •Female patients who are pregnant or lactating or are unwilling to use effective methods of contraception.
- •Patients with known adverse reaction to J147 or its components.
- •Patients previously enrolled in this clinical study. Specific Neuroimaging Exclusion Criteria
- •Computed tomography (CT) or MRI evidence of acute intracranial hemorrhage (the presence of chronic microbleeds is allowed).
- •Significant mass effect with midline shift.
- •Imaging evidence or history of intracranial neoplasms except for meningiomas.
研究组 & 干预措施
Target Dose Placebo
干预措施: Placebo (Other)
Target Dose J147
J147 Emulsion for Injection
干预措施: J147 Emulsion for Injection (Drug)
Low Dose J147
J147 Emulsion for Injection, 1.6 mg/kg
干预措施: J147 Emulsion for Injection (Drug)
Low Dose Placebo
干预措施: Placebo (Other)
High Dose J147
J147 Emulsion for Injection, 2.5 mg/kg
干预措施: J147 Emulsion for Injection (Drug)
High Dose Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Safety of J147 Emulsion for Injection (J147) when administered with endovascular therapy in acute ischemic stroke patients.
时间窗: From enrollment to end of study at 90 days.
Continuous vital signs, 12-Lead ECG, and laboratory assessments will be summarized using descriptive statistics, which includes count, mean, median, standard deviation, min and max by treatment arm and visits. Incidence and severity of adverse events and serious adverse events will be summarized with count and percentages by treatment arm, overall and by System Organ Class and Preferred Term. Deaths will be listed.
Safety of J147 Emulsion for Injection (J147) when administered with endovascular therapy ± intravenous thrombolytic agent in acute ischemic stroke patients.
时间窗: From enrollment to end of study at 90 days.
Continuous vital signs, 12-Lead ECG, and laboratory assessments will be summarized using descriptive statistics, which includes count, mean, median, standard deviation, min and max by treatment arm and visits. Incidence and severity of adverse events and serious adverse events will be summarized with count and percentages by treatment arm, overall and by System Organ Class and Preferred Term. Deaths will be listed.
次要结局
- Change from baseline (MRI at 2 h post dose) in MRI infarct volumes at 72 h ± 6 h.(72 hours)
- Change from baseline (MRI at 2 h post dose) in MRI infarct volumes measured at 30 ± 7 days(30 days)
- Change from baseline in MRI infarct volumes measured at 30 ± 7 days(30 days)
- 72 h NIHSS Score(72 hours)
- 90 day mRS Score(90 days)
- Change from baseline in MRI infarct volumes at 24 h(24 hours)