A Double-Blind, Placebo-Controlled, Randomized, Phase Ib/IIa Clinical Study of ApTOLL for the Treatment of Acute Ischemic Stroke
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 151
- 试验地点
- 16
- 主要终点
- Safety of ApTOLL
研究概览
简要总结
This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke patients who are candidates to receive reperfusion therapies.
详细描述
This is a prospective, multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to assess the administration of ApTOLL together with endovascular therapy in acute ischemic stroke (AIS) patients with confirmed Large Vessel Occlusion (LVO) who are candidates to receive reperfusion therapies including endovascular treatment with or without i.v. rt-PA (recombinant tissue Plasminogen Activator).
The study will be a Phase Ib/IIa trial where 2 doses selected, based on safety criteria, on Phase Ib will be administered in the following Phase IIa.The objective of the study is to evaluate if administration of ApTOLL at different doses is safe and well tolerated compared to placebo when administered with endovascular therapy (EVT), with or without i.v. rt-PA, 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
- •Age ≥18 and ≤90 years.
- •Informed consent obtained from subject or acceptable subject surrogate (i.e. next of kin, or legal representative).
- •A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
- •Baseline NIHSS obtained prior to randomization ≥ 8 points and ≤ 25 points.
- •Pre-stroke mRS score of 0 -
- •Treatable as soon as possible and at least within 6 hours of symptom onset, defined as point in time when the subject was last seen well (at baseline).
- •Patients should be candidates to receive EVT treatment with or without i.v. rt-PA.
- •Occlusion (TICI 0 or TICI 1 flow), of the terminal internal carotid artery (TICA), M1 or M2 segments of the middle cerebral artery, suitable for mechanical embolectomy, confirmed on Computed Tomography Angiography.
- •The following imaging criteria should also be met on admission neuroimaging:
- •MRI criterion: volume of DWI (Diffusion-weighted Imaging) restriction ≥5 mL and ≤70 mL OR
- •CT criterion: Alberta Stroke program early CT score (ASPECTS) 6 to 10 on baseline CT AND infarct core determined on admission CTPerfusion by Cerebral Blood Flow<30%: ≥5 mL and ≤70 mL.
- •The subject has an indication and is planned to receive endovascular treatment of stroke according to the European Stroke Organization Guidelines.
排除标准
- •Subject has suffered a stroke in the past 1 year.
- •Occlusion (TICI 0 or TICI 1 flow) of the basilar or vertebral or posterior or anterior cerebral arteries.
- •Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
- •Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR (international normalized ratio)>3.
- •Baseline platelet count <50,000/μL.
- •Baseline blood glucose of <50 mg/dL or >400 mg/dL.
- •Severe, sustained hypertension (systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg).
- •Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.
- •Subjects with identifiable intracranial tumors.
- •History of life-threatening allergy (more than rash) to contrast medium.
- •Known renal insufficiency with creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) <30 mL/min.
- •Cerebral vasculitis.
- •Evidence of active systemic infection.
- •Known current use of cocaine at time of treatment.
- •Patient participating in a study involving an investigational drug or device that would impact this study.
- •Patients that are unlikely to be available for a 90-day follow-up (e.g. no fixed home address, visitor from overseas).
- •Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
- •CT or MRI evidence of hemorrhage (the presence of microbleeds is allowed).
- •Significant mass effect with midline shift.
- •Suspicion of aortic dissection presumed septic embolus, or suspicion of bacterial endocarditis.
研究组 & 干预措施
Phase Ib ApTOLL
ApTOLL is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include six patients.
干预措施: ApTOLL (Drug)
Phase Ib Placebo
Placebo is administered intravenously in a single ascending dose pattern in four dose levels (0.025mg/kg - 0.2mg/kg). All levels include two patients.
干预措施: Placebo (Other)
Phase IIa ApTOLL
ApTOLL is administered intravenously (two doses selected in Phase Ib). The two dose levels include 35 patients each one.
干预措施: ApTOLL (Drug)
Phase IIa Placebo
Placebo is administered intravenously in one arm which includes 49 patients.
干预措施: Placebo (Other)
结局指标
主要结局
Safety of ApTOLL
时间窗: From dosing to follow-up (day 90 after dosing)
To assess if ApTOLL is safe when combined with EVT therapy as determined by: 1. Death. 2. Adverse events that occur during the study. 3. Physical examination. 4. Laboratory tests. 5. Recurrent stroke. 6. Symptomatic intracranial hemorrhage (sICH).
次要结局
- Mean infarct volume(72 hours)
- Early clinical course(72 hours post-dose)
- Effect in inflammatory response(Predose and up to 72 hours post-dose)
- Long-term outcome(Day 90 post-dose)