the effect of gd-iexo-003 in acute ischemic stroke

Conditions: Acute Ischemic Stroke

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.

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 criteria:
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.

Keywords: exosome