ExoCURE: The Effect of GD-iExo-003 in Acute Ischemic Stroke
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
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 20μg/kg; cohort 2 40μg/kg and cohort 3 80μg/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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: exosomes derived from human induced pluripotent stem cell for injection
Exosomes derived from human induced pluripotent stem cell for injection (3.0ml, protein concentration 1mg/mL).
Other Names:
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| Placebo Comparator: 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. |
Drug: a placebo of exosomes derived from human induced pluripotent stem cell for injection
Exosomes placebo, 3.0ml
Other Names:
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Outcome Measures
Primary Outcome Measures
- Number of participants who experienced dose-limiting Toxicities (DLTs) [14±2 days]
DLTs related to exosome is defined as any of the following: (1) Grade 3-4 infusion-related allergic adverse events consisting of perturbation of cardiovascular, respiratory function, or allergic reactions occurring in the first 24h postinfusion of investigational product; (2) grade 3-4 adverse events through seven days after administration of the last injection; (3) neurologic worsening defined as a 4-point increase in NIHSS compared with baseline NIHSS assessed through seven-days after administration of the last injection; and (4) rate of intracranial hemorrhage. Adverse event is graded in Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).
Secondary Outcome Measures
- Incidence of severe adverse events [90±7 days]
The proportion of patients who experienced severe adverse events.
- 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 [7 days]
The change of National Institutes of Health Stroke Scale (NIHSS) score of day 7 to baseline.
- 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
Other Outcome Measures
- Change of infarct volume [14±2 days]
The infarct volume is measured by CT or MRI from the baseline to 14 days
- Blood marker changes from baseline to discharge [at discharge, an average of 14 days]
A number of blood markers will be examined including C-reactive protein, glial fibrillary acidic protein, IL-1β, IL-6, IL-8, IL-10, Tumor Necrosis Factor-alpha.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Clinical diagnosis of acute ischemic stroke
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Age 18-70 years, inclusion of both genders
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Modified Rankin Scale score before stroke of 0-1
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NIHSS score 6-20 at inclusion that did not change by ≥4 points from screening to baseline assessment.
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Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
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Confirmation of hemispheric cortical infarct with magnetic resonance imaging or computed tomography
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Subjects who received intravenous thrombolysis or underwent mechanical reperfusion are eligible if they meet all other eligibility criteria.
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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
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Adequate cardiac function.
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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:
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Presence of intracranial hemorrhage on CT including hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage or hemorrhagic transformation, etc.
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Presence of a lacunar or a brainstem infarct as the etiology of current symptoms.
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Evidence of brain tumor or history of epilepsy or traumatic brain injury.
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Subjects with present malignant disease.
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Subjects with severe comorbidities including immunodeficiency or coagulation disorders.
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Subjects with Alzheimer's disease, Parkinson's disease or other degenerative neurological disease.
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Ongoing systemic infection, severe local infection or taking immunosuppressants.
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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
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Allergy to the study products.
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Documented allergies
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Participation in any clinical trial in the last 3 months
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Inability or unwillingness to comply with the study schedule
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Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible), oe breast feeding
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Other serious medical or psychiatric illness that is not adequately controlled
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Other circumstances that the investigator considers inappropriate for participation in the trial.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Xuanwu Hospital, Beijing
- Guidon Pharmaceutics Ltd.
Investigators
- Principal Investigator: Junwei Hao, MD; PhD, Xuanwu Hospital, Beijing
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XMEC-2023-004