Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 negative 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.