The Effect of Exosomes Derived From Human Induced Pluripotent Stem Cell (GD-iExo-003) in Acute Ischemic Stroke: an Exploratory Study.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Incidence of serious adverse events
研究概览
简要总结
This is a multicenter, randomized, double-blinded, placebo-controlled, dose-escalation trial. The objective of this study is evaluating safety and preliminary efficacy of intravenous exosomes derived from human induced pluripotent stem cell (GD-iExo-003) in acute ischemic stroke.
详细描述
This is a multicenter, randomized, double-blinded, placebo-controlled, dose-escalation trial. This study will consist of 2 parts, with part 1 being a dose-escalation study and part 2 being an expanded safety study based on part 1 findings.
A traditional 3+3 dose escalation design will be implemented in part 1. Cohort 1: receive 2×10^9 particles/kg; cohort 2: 4×10^9 particles/kg and cohort 3: 8×10^9 particles/kg. If no dose-limiting toxicities (DLTs) are observed for 2 weeks after administration of the first injection, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in 1 participant in the cohort, another 3 participants will be treated in the same dose level. Dose escalation will be stopped until DLTs are observed in >33% of the participants.
In part 2, 20 subjects will be randomized in a 1:1 ratio [exosome (n=10) or exosome placebo (n=10)]. The dose level will be determined by Data Safety Monitoring Board based on part 1.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of acute ischemic stroke
- •Age 18-70 years, inclusion of both genders
- •Modified Rankin Scale score before stroke of 0-1
- •NIHSS score 6-20 at inclusion that did not change by ≥4 points from screening to baseline assessment.
- •Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
- •Confirmation of hemispheric cortical infarct with magnetic resonance imaging or computed tomography
- •Subjects who received intravenous thrombolysis or underwent mechanical reperfusion are eligible if they meet all other eligibility criteria.
- •Adequate hepatic and renal function: serum aspartate aminotransferase ≤2.5× upper limit of normal; serum alanine aminotransferase ≤2.5× upper limit of normal; blood urea nitrogen ≤1.25× upper limit of normal; serum creatinine ≤1.25× upper limit of normal
- •Adequate cardiac function.
- •Subjects or legal representative can sign the informed consent and must be willing and able to comply with all aspects of treatment and follow-up schedule.
排除标准
- •Presence of intracranial hemorrhage on CT including hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage or hemorrhagic transformation, etc.
- •Presence of a lacunar or a brainstem infarct as the etiology of current symptoms.
- •Evidence of brain tumor or history of epilepsy or traumatic brain injury.
- •Subjects with present malignant disease.
- •Subjects with severe comorbidities including immunodeficiency or coagulation disorders.
- •Subjects with Alzheimer's disease, Parkinson's disease or other degenerative neurological disease.
- •Ongoing systemic infection, severe local infection or taking immunosuppressants.
- •Subjects with positive hepatitis B surface antibody (HBsAg) and positive hepatitis B core antibody (HBcAb), or HBsAg-positive virus carriers, positive hepatitis C antibody, positive syphilis antibody or HIV
- •Allergy to the study products.
- •Documented allergies
- •Participation in any clinical trial in the last 3 months
- •Inability or unwillingness to comply with the study schedule
- •Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible), oe breast feeding
- •Other serious medical or psychiatric illness that is not adequately controlled
- •Other circumstances that the investigator considers inappropriate for participation in the trial.
研究组 & 干预措施
Exosomes placebo group
Patients in this arm will be given a placebo of exosomes derived from human induced pluripotent stem cell for injection once a day for 7 days.
干预措施: a placebo of exosomes derived from human induced pluripotent stem cell for injection (Drug)
Exosomes group
Patients in this arm will be given exosomes derived from human induced pluripotent stem cell for injection once a day for 7 days.
干预措施: exosomes derived from human induced pluripotent stem cell for injection (Drug)
结局指标
主要结局
Incidence of serious adverse events
时间窗: 90±7 days
The proportion of patients who experienced serious adverse events.
Incidence of severe adverse events
时间窗: 90±7 days
The proportion of patients who experienced severe adverse events.
次要结局
- Favorable functional outcome(90±7 days)
- Functional outcome(90±7 days)
- NIHSS score change(14±2 days)
- Quality of Life (EQ-5D-5L)(90±7 days)
- Barthel Index (BI)(90±7 days)
- Favorable functional outcome(90±7 days)
- Functional outcome(90±7 days)
- NIHSS score change(90±7 days)
- Quality of Life (EQ-5D-5L)(90±7 days)
- Barthel Index (BI)(90±7 days)
- MoCA(90±7 days)
研究者
Junwei Hao, MD
Director of Neurology Department
Xuanwu Hospital, Beijing