Acute Ischemic Stroke
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety of B2065, an allogeneic adipose-derived mesenchymal stromal cell (AD-MSC) injection. It will also assess whether B2065 works to treat acute ischemic stroke. The main questions it aims to answer are: At what dose range is the drug safe for participants? Which dose shows preliminary efficacy? Researchers will compare B2065 to a placebo (a look-alike substance that contains no drug) to see if B2065 works to treat acute ischemic stroke. Participants will: Receive a single dose of B2065 during hospitalization Visit the hospital as scheduled for safety and efficacy assessments
Interventions
DRUGB2065
Administered by intravenous infusion.
DRUGPlacebo
Administered by intravenous infusion.
Sponsors
Tasly Pharmaceutical Group Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) [Safety] | Within 28 days after dosing. | Percentage of participants experiencing DLTs during the Phase 1 dose-escalation stage. |
| Incidence of Infusion-Related Reactions [Safety] | Within 7 days, 14 days, and 28 days. | Percentage of participants experiencing infusion-related reactions, including hypersensitivity reactions and systemic complications. |
| All-Cause Mortality Rate [Safety] | Within 14 days,12 months, and 24 months. | Proportion of participants who die from any cause during the study period. |
| Incidence of abnormal imaging findings indicative of tumorigenicity [Safety] | Month 6 and month 24. | Percentage of participants with newly detected tumorous lesions as assessed by chest and abdominal CT scans. |
| Change from baseline in serum tumor marker levels [Safety] | Change from baseline at Month 6 and Month 24. | Evaluation of serum levels of tumor markers |
| Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) [Safety] | Day1 to month 24 post-dose. | Percentage of participants experiencing one or more TEAEs, serious adverse events (SAEs), or adverse events leading to study discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving a modified Rankin Scale (mRS) score of 0-2 [Efficacy] | Day 28, day 90, month 6, and month 12. | Percentage of participants achieving functional independence (mRS score 0-2). The mRS is a 7-level scale ranging from 0 (no symptoms) to 6 (death). |
| Proportion of participants achieving a modified Rankin Scale (mRS) score of 0-1 [Efficacy] | Day 28, day 90, month 6, and month 12. | Percentage of participants achieving a favorable clinical outcome (mRS score 0-1). |
| Proportion of participants with neurological improvement based on NIH Stroke Scale (NIHSS) [Efficacy] | 24 hours, day 3, day 7, day 14, and month 12. | Percentage of participants with a decrease in NIHSS score of ≥4 points from baseline, or achieving an absolute NIHSS score ≤1. |
| Change from baseline in NIH Stroke Scale (NIHSS) score [Efficacy] | 24 hours, day 3, day 7, day 14, and month 12. | Quantitative assessment of neurological deficit changes from baseline. Scores range from 0 (no deficit) to 42 (severe deficit). |
| Proportion of participants achieving a Barthel Index (BI) score of 95-100 [Efficacy] | Day 28, day 90, month 6, and month 12. | Percentage of participants with slight or no disability (BI score 95-100). Total score ranges from 0 (complete dependence) to 100 (independence). |
| Change from baseline in EQ-5D-5L Index Score [Quality of Life] | Day 28, day 90, month 6, and month 12. | Standardized measure of health status across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). |
Countries
China
Outcome results
None listed