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

Tasly Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Ischemic Stroke

Treatments: Drug: B2065; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07371624

TSL-BM-B2065-I/IIa

Details and patient eligibility

About

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.

Enrollment: 54 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Aged 18 to 75 years (inclusive of the boundary values), with no restriction on sex.
2. Patients with ischemic stroke confirmed by imaging examinations (CT/MRI).
3. 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).
4. NIHSS score at screening is 8 to 20.
5. The patient or legally authorized representative is willing to participate in this trial and agrees to sign the informed consent form.

Exclusion Criteria

1. Patients who have received intravenous thrombolysis and/or mechanical thrombectomy prior to dosing.

2. Modified Rankin Scale (mRS) score ≥2 before stroke onset.

3. 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.

4. Patients who are unable to undergo CT and/or MRI examinations.

5. Patients with decreased level of consciousness (NIHSS item 1a score ≥2).

6. Patients who may have major neurologic or psychiatric disorders that seriously interfere with the participant's compliance with trial assessments.

7. Body temperature >38°C prior to dosing, and the investigator assesses that there is a risk of infection.

8. 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.

9. Patients with current or prior severe diseases of other organ systems, including but not limited to:

   1. Patients with severe heart failure (NYHA Class III or IV) and/or severe respiratory failure;
   2. Patients with renal disease with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²;
   3. Advanced liver disease, such as hepatitis or liver cirrhosis;
   4. 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);
   5. Patients with hypertension not controlled after taking therapeutic medications, with systolic blood pressure ≥185 mmHg and/or diastolic blood pressure ≥110 mmHg;
   6. Blood glucose <2.8 mmol/L (50 mg/dL) or >22.2 mmol/L (400 mg/dL).

10. Screening laboratory tests meeting any of the following criteria:

    1. Serum alanine aminotransferase (ALT) ≥3× upper limit of normal (ULN);
    2. Serum aspartate aminotransferase (AST) ≥3× ULN;
    3. Serum creatinine (Cr) ≥2× ULN;
    4. Absolute neutrophil count (ANC) <1.5×10^9/L;
    5. Platelet count (PLT) <100×10^9/L;
    6. Hemoglobin (Hgb) <90 g/L;
    7. International normalized ratio (INR) >1.7 or activated partial thromboplastin time (APTT) >1.25× ULN.

11. Patients with malignant tumors or other diseases with an expected survival of less than 2 years.

12. Patients with other acquired or congenital immunodeficiency diseases, or those currently using immunosuppressants.

13. Patients who, upon screening inquiry, have alcohol dependence or a history of drug abuse.

14. 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.

15. Patients who participated in any other clinical trial within 1 month prior to screening.

16. Patients who are allergic to any component of the investigational product.

17. Patients deemed by the investigator to be unsuitable for participation in this trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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54 participants in 2 patient groups, including a placebo group

B2065

Experimental group

Description:

Phase I dose escalation includes 5.0×10\^7 cells (1 bag), 1.5×10\^8 cells (3 bags), and 4.5×10\^8 cells (9 bags), formulated in 1% human serum albumin and sodium chloride injection. Phase IIa dose expansion will select 1-2 dose cohorts from Phase I. Participants will be randomized in a 2:1 ratio (B2065:placebo).

Treatment:

Drug: B2065

Placebo

Placebo Comparator group

Description:

Placebo (1% human serum albumin in sodium chloride injection) administered by intravenous infusion, with matched volume and number of bags.

Treatment:

Drug: Placebo