Clinical trial NCT06138210: The Effect of GD-iExo-003 in Acute Ischemic Stroke
Official title: The Effect of Exosomes Derived From Human Induced Pluripotent Stem Cell (GD-iExo-003) in Acute Ischemic Stroke: an Exploratory Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Ischemic Stroke
Keywords: exosome
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Guidon Pharmaceutics Ltd.
First posted: 2023-11-18
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of participants who experienced dose-limiting Toxicities (DLTs)
timeFrame: 14±2 days
Secondary outcomes:
measure: Incidence of severe adverse events
timeFrame: 90±7 days
measure: Favorable functional outcome
timeFrame: 90±7 days
measure: Functional outcome
timeFrame: 90±7 days
measure: NIHSS score change
timeFrame: 7 days
measure: NIHSS score change
timeFrame: 14±2 days
measure: Quality of Life (EQ-5D-5L)
timeFrame: 90±7 days
measure: Barthel Index (BI)
timeFrame: 90±7 days
Other outcomes:
measure: Change of infarct volume
timeFrame: 14±2 days
measure: Blood marker changes from baseline to discharge
timeFrame: at discharge, an average of 14 days
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Junwei Hao, MD; PhD
role: PRINCIPAL_INVESTIGATOR
References: