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

Phase 1Not Yet RecruitingNCT07628933

BOE Technology Group Co., Ltd.35 enrolled

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

Placebo of Human Umbilical Cord Mesenchymal Stromal Cells InjectionDRUG

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.

Human Umbilical Cord Mesenchymal Stem Cells InjectionDRUG

the first phase (Phase Ia) is a single-dose administration

Human Umbilical Cord Mesenchymal Stem Cells InjectionDRUG

the second phase (Phase Ib) is a multiple-dose administration.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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 Outcomes

Proportion of participants with an Modified Rankin Scale (mRS) score of 0-2

The modified Rankin Scale (mRS) is a widely used clinical outcome measure that assesses the degree of disability or dependence in the daily activities of patients who have suffered a stroke or other neurological conditions. It is a simple, 7-level ordinal scale ranging from 0 to 6: 0 - No symptoms at all. 1. \- No significant disability: able to perform all usual activities despite some symptoms. 2. \- Slight disability: unable to carry out all previous activities but able to look after own affairs without assistance. 3. \- Moderate disability: requires some help but able to walk without assistance. 4. \- Moderately severe disability: unable to walk or attend to bodily needs without assistance. 5. \- Severe disability: bedridden, incontinent, requiring constant nursing care. 6. \- Dead. A higher score indicates more severe disability. The mRS is the most common primary endpoint in acute stroke clinical trials, with a score of 0-2 at 90 days often defined as a "good outcome.

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

The National Institutes of Health Stroke Scale (NIHSS) is a standardized tool used to objectively quantify the severity of neurological deficits in patients with stroke. It consists of 15 items, including assessments of consciousness, eye movements, visual fields, facial palsy, motor and sensory function, language, speech, and neglect. Each item is scored, with a total score ranging from 0 to 42. Higher scores indicate more severe neurological impairment. The NIHSS is widely used in clinical practice and research to evaluate stroke severity, guide treatment decisions, and predict patient outcomes.

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

The Barthel Index (BI) is a standardized ordinal scale used to measure a person's performance in activities of daily living (ADL). It assesses 10 basic functions, including feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, transfers (e.g., bed to chair), mobility, and stair climbing. Each item is scored based on the amount of physical assistance required, with total scores typically ranging from 0 to 100 (or 0-20 in some versions). It is widely used in geriatrics, rehabilitation, and stroke research to evaluate functional independence and track changes over time.A higher Barthel Index score indicates greater functional independence (less need for assistance), while a lower score reflects greater disability and dependency. For example, a score of 100 means the patient is fully independent in basic ADL.

Time frame: Day 30, Day 90, Day180, Day360

Change from baseline in the Fugl-Meyer Motor Function Assessment Scale score

The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index widely recognized as a gold standard scale for evaluating sensorimotor recovery in patients with post-stroke hemiplegia. A higher FMA score indicates better motor function and less impairment, reflecting more positive outcomes in stroke recovery. For example, the motor domain score ranges from 0 (complete hemiplegia) to 100 (normal motor performance). The total FMA score is therefore a direct measure of functional recovery: the higher the score, the greater the improvement in sensorimotor function following stroke.

Time frame: Day 30, Day90, Day180, Day 360

Change from baseline in objective imaging findings （CT/MRI)

Time frame: Day 90