A Phase I Trial of Umbilical Cord Mesenchymal Stromal Cells for Acute Ischemic Stroke

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Human Umbilical Cord-derived Mesenchymal Stromal Cell Injection in Patients With Acute Ischemic Stroke (AIS)

Study Methods: The trial consists of two phases, both including a placebo control.

Phase Ia (single-dose, dose-escalation): Three dose groups (low, medium, high) are set. This is a multicenter, randomized, double-blind, placebo-controlled, single-dose, dose-escalation trial. Dose escalation to the next level is permitted only after safety assessment at 28 days post-dose in the previous group.

Phase Ib (multiple-dose): Based on Phase Ia results, two dose groups will be selected. The product is administered on Day 0, Day 7, and Day 14 (3 doses total). The trial remains randomized, double-blind, and placebo-controlled.

Objective of this study: To preliminarily evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stromal cell injection in the treatment of AIS.

Study methods: This trial is divided into two phases, both including a placebo control.

Phase I (Ia): A multicenter, randomized, double-blind, placebo-controlled, single-dose, dose-escalation trial. Three dose groups are set: low dose (5.0×10⁷ cells), medium dose (1.0×10⁸ cells), and high dose (2.0×10⁸ cells). The low-dose group enrolls 3-6 participants (all receiving the investigational product, with the first of the first 3 participants as a sentinel). The medium- and high-dose groups each enroll 8 participants (2 sentinels receiving the investigational product, and the remaining 6 randomized in a 2:1 ratio to the investigational product or placebo group). Phase Ia plans to enroll 19-22 participants. Dose escalation to the next dose group is permitted only after all participants in the previous dose group have completed dosing and been observed for at least 28 days with a favorable safety assessment.

Phase Ib: A multicenter, randomized, double-blind, placebo-controlled, dose-escalation, multiple-dose trial. Based on the results of Phase Ia, two dose groups will be selected. The initial plan is to administer the product on Day 0, Day 7, and Day 14 (3 doses in total). Each dose group enrolls 8 participants (6 receiving the investigational product, 2 receiving placebo), for a total of 16 participants. Escalation to the next higher dose group is permitted only after all participants in the previous dose group have completed the three doses and been observed for at least 28 days with a favorable safety assessment.

Study duration: 720 days

Inclusion Criteria:

• Age ≥18 years, both genders included.
• Clinical diagnosis of anterior circulation ischemic stroke, and able to receive the investigational product within 48 hours after the onset of stroke symptoms.
• National Institutes of Health Stroke Scale (NIHSS) score of 6-20 (inclusive), with a score of <2 on item Ia of the NIHSS.
• Pre-stroke modified Rankin Scale (mRS) score ≤1.
• The participant voluntarily agrees to participate in this study, signs the informed consent form personally or via a legal guardian, and has good compliance.

Exclusion Criteria:

• Planned or already performed thrombectomy for the current stroke.

• Treatment with neuroprotective agents after the current stroke.

• History of cerebral hemorrhage, subarachnoid hemorrhage, or hemorrhagic transformation after the current ischemic stroke, and judged by the investigator to be unsuitable for participation in the clinical trial.

• Uncontrolled systemic diseases, including but not limited to: hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure ≥100 mmHg), diabetes mellitus (acute diabetic complications such as ketoacidosis, hyperglycemic hyperosmolar state, lactic acidosis, or hypoglycemic coma within the past 3 months, or glycated hemoglobin >8.5%, or poorly controlled blood glucose [blood glucose >16.8 mmol/L or <2.8 mmol/L]), renal disease (eGFR <30 mL/min), liver failure (Child-Pugh Class C), severe heart failure (New York Heart Association [NYHA] Class IV), severe chronic respiratory disease.

• Organ function meeting any one or more of the following criteria:

  1. Absolute neutrophil count (ANC) <1.5×10⁹/L, platelet count (PLT) <100×10⁹/L, hemoglobin (Hb) <90 g/L;
  2. Aspartate aminotransferase (AST) >2.5× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >2.5×ULN, serum total bilirubin (TBIL) >1.5×ULN;
  3. Creatinine (Cr) >1.5×ULN;
  4. For patients not receiving anticoagulant or antithrombotic therapy: international normalized ratio (INR) >1.7 or activated partial thromboplastin time (APTT) >1.25×ULN; for patients receiving anticoagulant or antithrombotic therapy: INR >3.0 or APTT >1.5×ULN.

• Diagnosis of immunodeficiency disease, or long-term use of immunosuppressants or systemic corticosteroids at high doses within a short period before screening.

• Epilepsy, Alzheimer's disease, Parkinson's disease, severe depression, or other neurological or psychiatric disorders that, in the investigator's opinion, could affect the participant's ability to participate in the trial or interfere with study assessments.

• Presence of autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.).

• Inability to undergo cranial CT/MRI examination for any reason (e.g., metallic implants such as cardiac pacemakers, claustrophobia, etc.).

• Participation in another clinical trial of an investigational drug within 3 months before screening.

• Pregnancy, breastfeeding, planned pregnancy, or inability to use effective contraceptive measures.

• Any other condition that, in the investigator's judgment, makes the participant unsuitable for inclusion in this study.