A Phase 3 Study to Evaluate the Efficacy and Safety of 3K3A-APC in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy, or Both in Subjects with Moderate to Severe Acute Ischemic Stroke
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 1,400
- 主要终点
- To evaluate the effect of 3K3A-APC on 90-day disability
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of intravenous doses of 3K3A-APC, a recombinant variant of human activated protein C (APC), in the treatment of acute ischemic stroke following treatment with thrombolysis, mechanical thrombectomy or both.
详细描述
This multicenter, randomized, placebo-controlled, double-blind, Phase 3 study is being performed in coordination with StrokeNet to evaluate efficacy and safety of 3K3A-APC following administration of thrombolysis, mechanical thrombectomy, or both in subjects with moderate to severe acute ischemic stroke.
The study will be conducted in two phases. During a lead-in dose-finding phase, a maximum of 360 subjects will be randomized to 3K3A-APC or placebo using a Bayesian adaptive approach. Randomized subjects will receive 3K3A-APC or placebo every 12 hours for up to 5 doses (approximately 3 days) or until discharge from the hospital (whichever occurs first). The lead-in phase will transition to one selected 3K3A APC dose-and recruitment will continue-when a single dose proves superior to all other doses and safe.
The definitive phase will continue with the selected dose of 3K3A-APC from the lead-in phase. Randomization will be stratified on 4 variables. Lead-in patients who received the dose selected for the definitive phase will be included in the final data analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Acute ischemic stroke
- •Able to receive thrombolysis, mechanical thrombectomy or both
- •National Institutes of Health Stroke Scale (NIHSS) score of ≥ 5
- •Signed informed consent
- •Agreement to use effective birth control throughout the study
排除标准
- •Neurologic deficit is non-disabling
- •History of stroke or penetrating head injury within 90 days prior to enrollment
- •History of previous or current diagnosis of intracranial hemorrhage
- •Moyamoya disease, cerebral arteriovenous malformation, or known unsecured aneurysm requiring intervention during the acute study period
- •Presence of tandem lesions suggesting a likely need for proximal artery stenting during the thrombectomy procedure that would mandate post-operative dual antiplatelet therapy
- •Presence of other neurological or non-neurological co-morbidities, independently of the current stroke, that may lead to further deterioration in the subject's neurological status during the study period
- •Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)
- •Severe hypertension or hypotension
- •Blood glucose concentration < 50 mg/dL
- •Prior exposure to any exogenous form of a recombinant variant of human APC
研究组 & 干预措施
10mg of 3K3A-APC
3K3A-APC, q12h for up to 5 doses
干预措施: 3K3A-APC (Biological)
15mg of 3K3A-APC
3K3A-APC, q12h for up to 5 doses
干预措施: 3K3A-APC (Biological)
30mg of 3K3A-APC
3K3A-APC, q12h for up to 5 doses
干预措施: 3K3A-APC (Biological)
Placebo
Matching placebo, q12h for up to 5 doses
干预措施: Placebo (Other)
结局指标
主要结局
To evaluate the effect of 3K3A-APC on 90-day disability
时间窗: Day 90 mRS
Day 90 mRS scores will be compared between groups using ordinal (shift) analysis
次要结局
- To evaluate the safety of 3K3A-APC(Baseline to Day 90)