A Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Intravenous Infusion of hUC-MSCs in Patients With AIS

A Phase IIa Randomized, Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Intravenous Infusion of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) in the Treatment of Acute Ischemic Stroke (AIS)

This is a Phase IIa clinical trial with a three-arm design that utilizes randomization, double-blinding, and placebo control. The primary objective of this study is to evaluate the efficacy of single and multiple intravenous infusions of hUC-MSCs injection in patients with AIS. The secondary objective is to assess the safety and tolerability of single and multiple intravenous infusions of hUC-MSCs injection in patients with AIS. The exploratory objective is to investigate the pharmacokinetic and pharmacodynamic characteristics of hUC-MSCs injection in patients with AIS.

Stroke is a disease with high incidence, disability rate, and mortality rate, ranking as the second leading cause of death globally and the leading cause in China. Acute ischemic stroke (AIS) accounts for approximately 60%-80% of all strokes. The most effective treatments for AIS are revascularization therapies within the time window, including intravenous thrombolysis with tissue plasminogen activator (t-PA) and mechanical thrombectomy. Although t-PA thrombolysis is effective, it can cause reperfusion injury, exacerbating a series of inflammatory damages. Additionally, the success rate of thrombolysis and thrombectomy is closely related to the onset time. The time window within 4.5 hours or 6 hours is considered effective for rescuing the ischemic penumbra, and only a minority of AIS patients can receive thrombolytic therapy. Some patients have contraindications to thrombolysis, and endovascular treatment is only suitable for large vessel occlusion. Furthermore, in China, low public awareness of early disease recognition, insufficient prehospital emergency capabilities, in-hospital emergency delays, and other factors lead to delayed AIS treatment and a low thrombolysis rate.

Studies have shown that mesenchymal stem cells can reduce the infarct area and alleviate blood-brain barrier damage by regulating the microenvironment of damaged brain tissue, alleviating inflammatory responses, and promoting angiogenesis, neurogenesis, and neurovascular repair. This study aims to evaluate the efficacy, safety, and tolerance of single and multiple intravenous infusions of hUC-MSCs injection in the treatment of AIS patients.

Inclusion Criteria:

1. Age 18 to 75 years, inclusive, regardless of gender.
2. Diagnosis of acute ischemic stroke (AIS).
3. Onset time ≤ 72 hours.
4. Anterior circulation cerebral infarction.
5. Modified Rankin Scale (mRS) score ≤ 1 before the onset of this stroke.
6. National Institutes of Health Stroke Scale (NIHSS) score between 8 and 20 (inclusive) at screening, and NIHSS item 1a (level of consciousness) score ≤ 1.
7. The subject or their legal guardian has signed the informed consent form.

Exclusion Criteria:

1. Planned or already undergone thrombolysis or thrombectomy for this stroke.
2. History of epilepsy (excluding secondary epilepsy that does not currently require medication), Parkinson's disease, Alzheimer's disease, severe depression, or other diseases that the investigator deems would affect the subject's participation in the trial or the assessment of efficacy.
3. Presence of intracranial hemorrhagic disease (e.g., intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma, etc.). If only petechial bleeding is present, the investigator may determine whether the subject is suitable for inclusion in the study.
4. Computed tomography (CT) or magnetic resonance imaging (MRI) of the head showing a large ischemic area in the middle cerebral artery territory or midline shift greater than 1 cm on head CT/MRI, and the investigator assesses a high likelihood of surgical intervention or poor prognosis.
5. Presence of brain tumor or history of malignancy.
6. Liver or kidney insufficiency during the screening period: Aspartate aminotransferase (AST) > 2.5 × upper limit of normal, alanine aminotransferase (ALT) > 2.5 × upper limit of normal, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m².
7. History of severe cardiovascular disease, which the investigator deems unsuitable for participation in this clinical trial.
8. Severe infection, including sepsis, septic shock, severe pneumonia, etc.
9. Systemic corticosteroid ( > 10 mg/day prednisone equivalent) or immunosuppressive drug treatment within 14 days before receiving the investigational drug or during the trial.
10. History of alcohol abuse within the past year (defined as an average of more than 2 units per day (1 unit = 10 mL ethanol, i.e., 1 unit = 200 mL of 5% alcohol beer or 25 mL of 40% alcohol spirits or 85 mL of 12% alcohol wine).
11. Pregnant or breastfeeding women; or unwillingness to use reliable contraception (e.g., condoms) throughout the study period, or plans to donate sperm or eggs, or have plans for pregnancy.
12. Participation in an interventional clinical trial within the past 3 months, or receipt of other cell therapy (excluding blood transfusion).
13. Other situations in which the investigator deems the patient unsuitable for participation in this study (including but not limited to non-compliance with the principle of patient benefit, poor patient compliance, unacceptable laboratory abnormalities, etc.).