Acute Ischemic Stroke
Conditions
Keywords
exosome
Brief summary
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.
Detailed 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.
Interventions
DRUGexosomes derived from human induced pluripotent stem cell for injection
Exosomes derived from human induced pluripotent stem cell for injection (3.0ml, 1×10\^11particles/ml).
Exosomes placebo, 3.0ml
Sponsors
Xuanwu Hospital, Beijing
Guidon Pharmaceutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious adverse events | 90±7 days | The proportion of patients who experienced serious adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Favorable functional outcome | 90±7 days | Rate of favorable functional outcome defined as a modified Rankin Scale (mRS, scores range from 0 to 6, with 0 to 2 indicating favorable outcome and 3 to 6 indicating unfavorable outcome including 6 as death) score of 0-2. |
| Functional outcome | 90±7 days | The range of mRS scores by shift analysis. |
| NIHSS score change | 14±2 days | The change of National Institutes of Health Stroke Scale (NIHSS) score of day 14 to baseline. |
| Quality of Life (EQ-5D-5L) | 90±7 days | The value of EQ-5D-5L score. |
| Barthel Index (BI) | 90±7 days | The value of BI |
| MoCA | 90±7 days | The value of MoCA |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJunwei Hao, MD; PhD
Xuanwu Hospital, Beijing
Outcome results
None listed