Clinical trial NCT06612710: The Safety and Efficacy of NouvSoma001 in Ischemic Stroke
Official title: An Open-label Exploratory Clinical Trial to Assess the Safety and Efficacy of NouvSoma001 in the Treatment of Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ischemic Stroke
Keywords: Ischemic Stroke
extracellular vesicles
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: iRegene Therapeutics Co., Ltd.
First posted: 2024-09-25
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a single-center, randomized, open-label, placebo-controlled, dose-escalation trial. The objective of this research is to evaluate the safety, tolerability, and preliminary efficacy of intravenous administration of human-induced neural stem cell-derived extracellular vesicles (NouvSoma001) in the treatment of ischemic stroke.

Detailed description: This is a single-center, randomized, open-label, placebo-controlled, dose-escalation trial. This study will consist of 2 parts, with Part 1 being a dose-escalation study and Part 2 being a dose-extension study based on the results of Part 1. Part 1 will follow a traditional 3+3 dose-escalation design, enrolling a total of 9 subjects. Cohort 1: receive 4×10\^9 particles/kg, Cohort 2: receive 8×10\^9 particles/kg, and Cohort 3: receive 1.6×10\^10 particles/kg. If no dose-limiting toxicities (DLT) are observed within 2 weeks after the initial administration, a new cohort will be enrolled at the next higher dose level. If DLTs are observed in 1 participant, another 2 participants will be treated at the same dose level. Dose escalation will cease if DLTs are observed in more than 33% of the participants. In Part 2, the remaining 60 participants will be randomized in a 2:1 ratio to the treatment and placebo groups, with the dose level determined by the Data Safety Monitoring Board based on the results of Part 1.

Eligibility criteria: Inclusion Criteria:

1. The age of the recruiters ranged from 18 to 75 years.
2. Clinical diagnosis of ischemic stroke, the time of stroke onset is known, and the onset occurred no more than 7 days before enrollment.
3. Magnetic resonance imaging (MRI) or computed tomography (CT) findings consistent with ischemic stroke.
4. At the time of enrollment, the NIHSS score is between 6 and 20; additionally, there is at least one limb with muscle strength ≤ Grade 3.
5. Patients who have the mental capacity to understand and participate in the study.
6. Informed consent was obtained from patients or their legal representatives.

Exclusion Criteria:

1. CT indicates intracranial hemorrhage, including hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, or hemorrhagic transformation.
2. Patients with Alzheimer's disease, Parkinson's syndrome, or other neurodegenerative disorders.
3. Evidence of brain tumors, epilepsy, or a history of traumatic brain injury.
4. Presence of non-vascular diseases causing white matter lesions, such as carbon monoxide poisoning, multiple sclerosis, or adrenoleukodystrophy.
5. Rapid spontaneous neurological improvement during the screening period, defined as a reduction of NIHSS score by ≥ 8 points from symptom onset to the first administration.
6. Persistent systemic infection, severe local infection, or ongoing use of immunosuppressants.
7. Patients with malignant diseases or an expected survival of less than 5 years.
8. Significant hearing or vision impairments, language disorders, or claustrophobia that would hinder cooperation with neuropsychological assessments and MRI examinations.
9. Contraindications to MRI.
10. Patients unable to comply with follow-up requirements during the study.
11. Severe liver, renal, cardiac, or pulmonary insufficiency, hematologic disorders, or malignant tumors (Liver insufficiency is defined as ALT or AST levels greater than 1.5 times the upper normal limit; renal insufficiency is defined as serum creatinine levels greater than 1.5 times the upper normal limit).
12. Patients with alcohol addiction or those testing positive for drug abuse.
13. Patients with a history of severe allergies or known allergy to human biological products.
14. Pregnant or breastfeeding women, and those planning to conceive during the trial period.
15. Participation in other clinical trials within the past 3 months.
16. Patients considered unsuitable for participation by the investigator.

Primary outcomes:
measure: The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
timeFrame: Up to 6 month after treatment initiation
Secondary outcomes:
measure: The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
timeFrame: Up to 18 month after treatment initiation
measure: Magnetic Resonance Imaging(MRI) at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The National Institutes of Health Stroke Scale, NIHSS
timeFrame: Up to 6 month after treatment initiation
measure: The Modified Rankin Scale (mRS)
timeFrame: Up to 6 month after treatment initiation
measure: The score of Mini-mental State Examination (MMSE) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Montreal cognitive assessment scale (MoCA) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Barthel Index for activities of daily living (ADL) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hamilton Depression Scale at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hamilton Anxiety Scale at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Clock Drawing Test at month 1、3、6 compared with baseline and control group
timeFrame: Up to 6 month after treatment initiation
measure: The value of Quality of Life (EQ-5D-5L) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Alzheimer's disease assessment scale-cognitive section (ADAS-cog) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Clinical Dementia Rating (CDR) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hopkins verbal learning test（HVLT）at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) events at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of Nfl and GFAP in serum at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University ofScience and Technology
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Wei Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Hospital
name: Daishi Tian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Hospital
name: Chuan Qin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang R, Mao W, Niu L, Bao W, Wang Y, Wang Y, Zhu Y, Yang Z, Chen J, Dong J, Cai M, Yuan Z, Song H, Li G, Zhang M, Xiong N, Wei J, Dong Z. NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice. Elife. 2023 Apr 27;12:e84493. doi: 10.7554/eLife.84493.
citation: Zhu ZH, Jia F, Ahmed W, Zhang GL, Wang H, Lin CQ, Chen WH, Chen LK. Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke. Neural Regen Res. 2023 Feb;18(2):404-409. doi: 10.4103/1673-5374.346466.
citation: Gao G, Li C, Ma Y, Liang Z, Li Y, Li X, Fu S, Wang Y, Xia X, Zheng JC. Neural stem cell-derived extracellular vesicles mitigate Alzheimer's disease-like phenotypes in a preclinical mouse model. Signal Transduct Target Ther. 2023 Jun 14;8(1):228. doi: 10.1038/s41392-023-01436-1. No abstract available.