The Effect of GD-iExo-003 in Acute Ischemic Stroke (ExoCURE)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: exosomes derived from human induced pluripotent stem cell for injection; Drug: a placebo of exosomes derived from human induced pluripotent stem cell for injection

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 Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gaoting Ma, MD; Phone Number: 18301579891; Email: demo_doctor@163.com
• Study Contact Backup: Name: Junwei Hao, MD; PhD; Phone Number: 010 8319 8277; Email: haojunwei@vip.163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: GD-iExo-003
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: GD-iExo-003 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe adverse events	The proportion of patients who experienced severe adverse events.	90±7 days
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
Functional outcome	The range of mRS scores by shift analysis.	90±7 days
NIHSS score change	The change of National Institutes of Health Stroke Scale (NIHSS) score of day 7 to baseline.	7 days
NIHSS score change	The change of National Institutes of Health Stroke Scale (NIHSS) score of day 14 to baseline.	14±2 days
Quality of Life (EQ-5D-5L)	The value of EQ-5D-5L score.	90±7 days
Barthel Index (BI)	The value of BI	90±7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of infarct volume	The infarct volume is measured by CT or MRI from the baseline to 14 days	14±2 days
Blood marker changes from baseline to discharge	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.	at discharge, an average of 14 days

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Guidon Pharmaceutics Ltd.
• Investigators: Principal Investigator: Junwei Hao, MD; PhD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): January 30, 2024
• Primary Completion (Estimated): August 30, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: November 12, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Estimated): November 20, 2023

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: exosome
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: XMEC-2023-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study will not share individual participant data to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No