The Effect of GD-iExo-003 in Acute Ischemic Stroke

Acute Ischemic Stroke Clinical Trial

— ExoCURE  

Official title:

The Effect of Exosomes Derived From Human Induced Pluripotent Stem Cell (GD-iExo-003) in Acute Ischemic Stroke: an Exploratory Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06138210
• Other study ID #: XMEC-2023-004
• Status: Recruiting
• Phase: Phase 1
• Start date: May 27, 2024
• Est. completion date: August 30, 2025

Study information

• Verified date: May 2024
• Source: Xuanwu Hospital, Beijing
• Contact: Junwei Hao, MD; PhD
• Phone: 010 8319 8277
• Email: haojunwei[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• exosomes 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).
• a placebo of exosomes derived from human induced pluripotent stem cell for injection
Exosomes placebo, 3.0ml

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing	Guidon Pharmaceutics Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of infarct volume	The infarct volume is measured by CT or MRI from the baseline to 14 days	14±2 days
Other	Blood marker changes from baseline to discharge	A number of blood markers will be examined including C-reactive protein, glial fibrillary acidic protein, IL-1ß, IL-6, IL-8, IL-10, Tumor Necrosis Factor-alpha.	at discharge, an average of 14 days
Primary	Number of participants who experienced dose-limiting Toxicities (DLTs)	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).	14±2 days
Secondary	Incidence of severe adverse events	The proportion of patients who experienced severe adverse events.	90±7 days
Secondary	Favorable functional outcome	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.	90±7 days
Secondary	Functional outcome	The range of mRS scores by shift analysis.	90±7 days
Secondary	NIHSS score change	The change of National Institutes of Health Stroke Scale (NIHSS) score of day 7 to baseline.	7 days
Secondary	NIHSS score change	The change of National Institutes of Health Stroke Scale (NIHSS) score of day 14 to baseline.	14±2 days
Secondary	Quality of Life (EQ-5D-5L)	The value of EQ-5D-5L score.	90±7 days
Secondary	Barthel Index (BI)	The value of BI	90±7 days