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

Official title

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)

Overview

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.

Detailed description

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

Interventions

• Drug Placebo of Human Umbilical Cord Mesenchymal Stromal Cells Injection
  Placebo refers to a cell-free product, whose packaging, storage conditions, expiration date, and method of administration remain consistent with those of the investigational drug.
• Drug Human Umbilical Cord Mesenchymal Stem Cells Injection
  the first phase (Phase Ia) is a single-dose administration
• Drug Human Umbilical Cord Mesenchymal Stem Cells Injection
  the second phase (Phase Ib) is a multiple-dose administration.

Primary outcome measures

• Incidence of DLT (Dose-Limiting Toxicity) events; [Time frame: Day28]
• All adverse events/serious adverse events during the trial; [Time frame: 2year]
• All-cause mortality [Time frame: Day90、Day180、Day360]

Secondary outcome measures (6)

• Proportion of participants with an Modified Rankin Scale (mRS) score of 0-2 [Time frame: Day 30, Day90, Day180, Day360]
• Proportion of participants with a ≥4-point improvement in National Institutes of Health Stroke Scale (NIHSS) score from baseline [Time frame: Day 7, Day 14, Day 30, Day 90, Day 180, Day 360]
• Change from baseline in National Institutes of Health Stroke Scale(NIHSS) score [Time frame: Day 7, Day 14, Day 30, Day 90, Day 180, Day 360]
• Proportion of participants with a Barthel Index ≥95 [Time frame: Day 30, Day 90, Day180, Day360]
• Change from baseline in the Fugl-Meyer Motor Function Assessment Scale score [Time frame: Day 30, Day90, Day180, Day 360]
• Change from baseline in objective imaging findings （CT/MRI) [Time frame: Day 90]

Eligibility criteria

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:

• Absolute neutrophil count (ANC) <1.5×10⁹/L, platelet count (PLT) <100×10⁹/L, hemoglobin (Hb) <90 g/L;
• 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;
• Creatinine (Cr) >1.5×ULN;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07628933 · YW2026-016-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗