The Effect of GD-iExo-003 in Acute Ischemic Stroke

Официальное название

The Effect of Exosomes Derived From Human Induced Pluripotent Stem Cell (GD-iExo-003) in Acute Ischemic Stroke: an Exploratory Study.

Обзор

This is a multicenter, randomized, double-blinded, placebo-controlled, dose-escalation trial. The objective of this study is evaluating safety and preliminary efficacy of intravenous exosomes derived from human induced pluripotent stem cell (GD-iExo-003) in acute ischemic stroke.

Подробное описание

This is a multicenter, randomized, double-blinded, placebo-controlled, dose-escalation trial. This study will consist of 2 parts, with part 1 being a dose-escalation study and part 2 being an expanded safety study based on part 1 findings.

A traditional 3+3 dose escalation design will be implemented in part 1. Cohort 1: receive 2×10\^9 particles/kg; cohort 2: 4×10\^9 particles/kg and cohort 3: 8×10\^9 particles/kg. If no dose-limiting toxicities (DLTs) are observed for 2 weeks after administration of the first injection, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in 1 participant in the cohort, another 3 participants will be treated in the same dose level. Dose escalation will be stopped until DLTs are observed in \>33% of the participants.

In part 2, 20 subjects will be randomized in a 1:1 ratio \[exosome (n=10) or exosome placebo (n=10)\]. The dose level will be determined by Data Safety Monitoring Board based on part 1.

Вмешательства

• Препарат exosomes derived from human induced pluripotent stem cell for injection
  Exosomes derived from human induced pluripotent stem cell for injection (3.0ml, 1×10\^11particles/ml).
• Препарат a placebo of exosomes derived from human induced pluripotent stem cell for injection
  Exosomes placebo, 3.0ml

Первичные конечные точки

• Incidence of severe adverse events [Срок оценки: 90±7 days]

Вторичные конечные точки (7)

• Favorable functional outcome [Срок оценки: 90±7 days]
• Functional outcome [Срок оценки: 90±7 days]
• NIHSS score change [Срок оценки: 14±2 days]
• NIHSS score change [Срок оценки: 90±7 days]
• Quality of Life (EQ-5D-5L) [Срок оценки: 90±7 days]
• Barthel Index (BI) [Срок оценки: 90±7 days]
• MoCA [Срок оценки: 90±7 days]

Критерии участия

Критерии включения

• Clinical diagnosis of acute ischemic stroke
• Age 18-70 years, inclusion of both genders
• Modified Rankin Scale score before stroke of 0-1
• NIHSS score 6-20 at inclusion that did not change by ≥4 points from screening to baseline assessment.
• Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
• Confirmation of hemispheric cortical infarct with magnetic resonance imaging or computed tomography
• Subjects who received intravenous thrombolysis or underwent mechanical reperfusion are eligible if they meet all other eligibility criteria.
• Adequate hepatic and renal function: serum aspartate aminotransferase ≤2.5× upper limit of normal; serum alanine aminotransferase ≤2.5× upper limit of normal; blood urea nitrogen ≤1.25× upper limit of normal; serum creatinine ≤1.25× upper limit of normal
• Adequate cardiac function.
• Subjects or legal representative can sign the informed consent and must be willing and able to comply with all aspects of treatment and follow-up schedule.

Критерии исключения

• Presence of intracranial hemorrhage on CT including hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage or hemorrhagic transformation, etc.
• Presence of a lacunar or a brainstem infarct as the etiology of current symptoms.
• Evidence of brain tumor or history of epilepsy or traumatic brain injury.
• Subjects with present malignant disease.
• Subjects with severe comorbidities including immunodeficiency or coagulation disorders.
• Subjects with Alzheimer's disease, Parkinson's disease or other degenerative neurological disease.
• Ongoing systemic infection, severe local infection or taking immunosuppressants.
• Subjects with positive hepatitis B surface antibody (HBsAg) and positive hepatitis B core antibody (HBcAb), or HBsAg-positive virus carriers, positive hepatitis C antibody, positive syphilis antibody or HIV
• Allergy to the study products.
• Documented allergies
• Participation in any clinical trial in the last 3 months
• Inability or unwillingness to comply with the study schedule
• Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible), oe breast feeding
• Other serious medical or psychiatric illness that is not adequately controlled
• Other circumstances that the investigator considers inappropriate for participation in the trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Xuanwu Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT06138210 · XMEC-2023-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗