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

Официальное название

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.

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (6)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07371624 · TSL-BM-B2065-I/IIa

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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