A Study of the Safety, Tolerability and Preliminary Efficacy of B2065 in Patients With Acute Ischemic Stroke.

Official title

A Phase I/IIa Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Allogeneic Adipose-Derived Mesenchymal Stromal Cell Injection (B2065) in Participants With Acute Ischemic Stroke.

Overview

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.

Interventions

• Drug B2065
  Administered by intravenous infusion.
• Drug Placebo
  Administered by intravenous infusion.

Primary outcome measures

• Incidence of participants with dose-limiting toxicity [Time frame: Within 28 days after dosing.]
• Infusion reactions [Time frame: Within 7 days, 14 days, and 28 days.]
• All-cause mortality [Time frame: Within 14 days,12 months, and 24 months.]
• Tumorigenicity surveillance [Time frame: Month 6 and month 24.]
• Adverse events (AEs) [Time frame: Day1 to month 24.]

Secondary outcome measures (6)

• Proportion of participants with an modified Rankin Scale score of 0-2 after treatment [Time frame: Day 28, day 90, month 6, and month 12.]
• Proportion of participants with an modified Rankin Scale score of 0-1 after treatment [Time frame: 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 [Time frame: 24 hours, day 3, day 7, day 14, and month 12.]
• Change from baseline in NIH Stroke Scale score after treatment [Time frame: 24 hours, day 3, day 7, day 14, and month 12.]
• Proportion of participants with a Barthel Index score of 95-100 after treatment [Time frame: Day 28, day 90, month 6, and month 12.]
• EQ-5D-5L score after treatment [Time frame: Day 28, day 90, month 6, and month 12.]

Eligibility criteria

Inclusion criteria

• 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.
• The patient or legally authorized representative is willing to participate in this trial and agrees to sign the informed consent form.

Exclusion criteria

• 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.
• Patients with decreased level of consciousness (NIHSS item 1a score ≥2).
• Patients who may have major neurologic or psychiatric disorders that seriously interfere with the participant's compliance with trial assessments.
• Body temperature >38°C prior to dosing, and the investigator assesses that there is a risk of infection.
• Patients with uncontrollable active infection; or patients who have received systemic anti-infective therapy within 7 days prior to dosing and, in the investigator's judgment, may be likely to convert to uncontrollable active infection in the short term.
• Patients with current or prior severe diseases of other organ systems, including but not limited to:

• Patients with severe heart failure (NYHA Class III or IV) and/or severe respiratory failure;
• Patients with renal disease with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²;
• Advanced liver disease, such as hepatitis or liver cirrhosis;
• Patients positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg); patients positive for hepatitis B e antibody (HBeAb) and/or hepatitis B core antibody (HBcAb) with quantitative HBV-DNA above the upper limit of normal; patients with any of the following test results positive: hepatitis C virus antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab), or human immunodeficiency virus antibody (HIV-Ab);
• Patients with hypertension not controlled after taking therapeutic medications, with systolic blood pressure ≥185 mmHg and/or diastolic blood pressure ≥110 mmHg;
• Blood glucose <2.8 mmol/L (50 mg/dL) or >22.2 mmol/L (400 mg/dL).
• Screening laboratory tests meeting any of the following criteria:

• Serum alanine aminotransferase (ALT) ≥3× upper limit of normal (ULN);
• Serum aspartate aminotransferase (AST) ≥3× ULN;
• Serum creatinine (Cr) ≥2× ULN;
• Absolute neutrophil count (ANC) <1.5×10\^9/L;
• Platelet count (PLT) <100×10\^9/L;
• Hemoglobin (Hgb) <90 g/L;
• International normalized ratio (INR) >1.7 or activated partial thromboplastin time (APTT) >1.25× ULN.
• Patients with malignant tumors or other diseases with an expected survival of less than 2 years.
• Patients with other acquired or congenital immunodeficiency diseases, or those currently using immunosuppressants.
• Patients who, upon screening inquiry, have alcohol dependence or a history of drug abuse.
• Pregnant or breastfeeding women; or those who plan to conceive, donate sperm, or donate oocytes during the trial and/or are unwilling to take effective contraception measures.
• Patients who participated in any other clinical trial within 1 month prior to screening.
• Patients who are allergic to any component of the investigational product.
• Patients deemed by the investigator to be unsuitable for participation in this trial.

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

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT07371624 · TSL-BM-B2065-I/IIa

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗