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.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicities (DLTs) [Safety]
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •The patient or legally authorized representative is willing to participate in this trial and agrees to sign the informed consent form.
排除标准
- •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.
研究组 & 干预措施
B2065
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).
干预措施: B2065 (Drug)
Placebo
Placebo (1% human serum albumin in sodium chloride injection) administered by intravenous infusion, with matched volume and number of bags.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities (DLTs) [Safety]
时间窗: Within 28 days after dosing.
Percentage of participants experiencing DLTs during the Phase 1 dose-escalation stage.
Incidence of Infusion-Related Reactions [Safety]
时间窗: 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]
时间窗: 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]
时间窗: 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]
时间窗: 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]
时间窗: 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.
Tumorigenicity surveillance
时间窗: Month 6 and month 24.
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).
Adverse events (AEs)
时间窗: Day1 to month 24.
Occurrence rate of AEs.
Incidence of participants with dose-limiting toxicity
时间窗: Within 28 days after dosing.
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
时间窗: Within 7 days, 14 days, and 28 days.
Infusion-related reactions include hypersensitivity reactions and systemic complications.
All-cause mortality
时间窗: Within 14 days,12 months, and 24 months.
次要结局
- Proportion of participants achieving a modified Rankin Scale (mRS) score of 0-2 [Efficacy](Day 28, day 90, month 6, and month 12.)
- Proportion of participants achieving a modified Rankin Scale (mRS) score of 0-1 [Efficacy](Day 28, day 90, month 6, and month 12.)
- Proportion of participants with neurological improvement based on NIH Stroke Scale (NIHSS) [Efficacy](24 hours, day 3, day 7, day 14, and month 12.)
- Change from baseline in NIH Stroke Scale (NIHSS) score [Efficacy](24 hours, day 3, day 7, day 14, and month 12.)
- Proportion of participants achieving a Barthel Index (BI) score of 95-100 [Efficacy](Day 28, day 90, month 6, and month 12.)
- Change from baseline in EQ-5D-5L Index Score [Quality of Life](Day 28, day 90, month 6, and month 12.)
- Proportion of participants with an modified Rankin Scale score of 0-2 after treatment(Day 28, day 90, month 6, and month 12.)
- Proportion of participants with an modified Rankin Scale score of 0-1 after treatment(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(24 hours, day 3, day 7, day 14, and month 12.)
- Change from baseline in NIH Stroke Scale score after treatment(24 hours, day 3, day 7, day 14, and month 12.)
- Proportion of participants with a Barthel Index score of 95-100 after treatment(Day 28, day 90, month 6, and month 12.)
- EQ-5D-5L score after treatment(Day 28, day 90, month 6, and month 12.)