This Phase I/IIa, randomized, double-blind, placebo-controlled study evaluates the safety, tolerability, and preliminary efficacy of B2065, an allogeneic adipose-derived mesenchymal stromal cell (AD-MSC) injection, in patients with acute ischemic stroke. Participants receive a single intravenous infusion of B2065 or placebo within 36 hours of stroke symptom onset. Phase I uses dose escalation with sentinel dosing to assess dose-limiting toxicities within 28 days and to inform dose selection. Phase IIa expands 1-2 selected dose level(s) and randomizes participants 2:1 (B2065:placebo). Safety and functional outcomes are assessed through 24 months.
Aged 18 to 75 years (inclusive of the boundary values), with no restriction on sex.
Patients with ischemic stroke confirmed by imaging examinations (CT/MRI).
Time from onset of stroke symptoms to administration of the investigational product ≤36 hours; for wake-up stroke, the time of onset is defined as the last-known-well time (the last time the patient was observed to be normal).
NIHSS score at screening is 8 to 20.
Patients who have received intravenous thrombolysis and/or mechanical thrombectomy prior to dosing.
Modified Rankin Scale (mRS) score ≥2 before stroke onset.
Patients who currently have intracranial hemorrhagic diseases (e.g., intracerebral hemorrhage, epidural hematoma, subarachnoid hemorrhage, etc.), or who have brain tumors, cerebrovascular malformations, multiple sclerosis, a history of severe traumatic brain injury, encephalitis, or other conditions causing stroke-like symptoms.
Patients who are unable to undergo CT and/or MRI examinations.
Parallel
B2065
DrugAdministered by intravenous infusion.
Placebo
DrugAdministered by intravenous infusion.
Incidence of participants with dose-limiting toxicity
Tolerability assessment (Phase l dose-escalation stage only). Dose-limiting toxicity (DLT) was defined as Grade ≥3 adverse events related to B2065 occurring within 28 days after dosing, assessed according to CTCAE (v6.0).
Infusion reactions
Infusion-related reactions include hypersensitivity reactions and systemic complications.
All-cause mortality
Tumorigenicity surveillance
Tumorigenicity assessments included chest and abdominal CT scans and tumor markers, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA199), squamous cell carcinoma antigen (SCCA), prostate-specific antigen (PSA), and neuron-specific enolase (NSE). Additional tumor markers assessed in female participants included carbohydrate antigen 15-3 (CA15-3), human chorionic gonadotropin (hCG), serum ferritin (SF), and beta-2 microglobulin (β2-MG).
Proportion of participants with an modified Rankin Scale score of 0-2 after treatment
The modified Rankin Scale (mRS) is used to assess functional recovery after stroke. The scale consists of 7 levels, ranging from 0 (no symptoms) to 6 (death). An mRS score of 0-1 is defined as a favorable clinical outcome, and an mRS score of 0-2 is defined as functional independence. The mRS will be assessed by investigators at screening/baseline, Day 28, Day 90, Month 6, and Month 12.
Proportion of participants with an modified Rankin Scale score of 0-1 after treatment
The modified Rankin Scale (mRS) is used to assess functional recovery after stroke. The scale consists of 7 levels, ranging from 0 (no symptoms) to 6 (death). An mRS score of 0-1 is defined as a favorable clinical outcome, and an mRS score of 0-2 is defined as functional independence. The mRS will be assessed by investigators at screening/baseline, Day 28, Day 90, Month 6, and Month 12.
Proportion of participants with a decrease in NIH Stroke Scale score of ≥4 points from baseline or an NIHSS score ≤1 after treatment
The NIH Stroke Scale (NIHSS) quantitatively evaluates the severity of neurological deficits in stroke patients, with scores ranging from 0 (no deficit) to 42 (most severe deficit). A decrease in NIHSS score of ≥4 points from baseline (or an NIHSS score ≤1) is defined as neurological improvement. The NIHSS will be assessed by investigators at each visit. The NIHSS score assessed within 20 minutes prior to dosing will be used as the baseline value.
Change from baseline in NIH Stroke Scale score after treatment
The NIH Stroke Scale (NIHSS) quantitatively evaluates the severity of neurological deficits in stroke patients, with scores ranging from 0 (no deficit) to 42 (most severe deficit). A decrease in NIHSS score of ≥4 points from baseline (or an NIHSS score ≤1) is defined as neurological improvement. The NIHSS will be assessed by investigators at each visit. The NIHSS score assessed within 20 minutes prior to dosing will be used as the baseline value.
Immune Biomarkers [Exploratory Outcome 1]
Immune Biomarkers (IgG, IgM, IgA, IgE; Treg; TNF-α).
Nerve Growth Factor [Exploratory Outcome 2]
Nerve Growth Factor (NGF).
Anti-drug Antibodies [Exploratory Outcome 3]
Anti-drug Antibodies (ADA).
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