A Phase I/IIa Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Multicenter, Blind, Randomized, Placebo Controlled Single Injection of It-hMSC in Patients With Ischemic Stroke
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events assessed by CTCAE V5.0 during the twelve-month study period after it-hMSC infusion.
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of single injection of it-hMSC in patients with ischemic stroke in a multicenter, blind, randomized, placebo controlled trial
详细描述
Stroke is a leading cause of disability. According to the comprehensive standardized prevalence estimation in 2016, 12.42 million people older than 40 years in China are currently suffering from stroke or have ever suffered from stroke. The overall prevalence rate of stroke in China was 1,596 per 100,000 people in 2016, 4.6 times higher than the rate of 345.1 per 100,000 people in 2013 and 70% of the survivors have disabilities in varying degrees. In addition to rehabilitation therapy, there is no therapeutic drugs of remarkable curative effect for the treatment of ischemic stroke patients. The latest data show that the annual recurrence rate of ischemic stroke in China is as high as 17.7%.
Allogeneic mesenchymal stem cells have been used in many clinical studies for different diseases. In addition to differentiating into multiple cell types and promoting the recovery and repair of the brain by replacing damaged cells, mesenchymal stem cells also secrete cytokines and neurotrophic factors to support and stimulate the growth of other endogenous cells. Meanwhile, mesenchymal stem cells also have anti-inflammatory and immunomodulatory functions. These characteristics of mesenchymal stem cells provide a new therapy for the treatment of stroke.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
In phase I, the masking method is open-label, whereas in phase II, the masking method is double blind.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older.
- •Clinical diagnosis of ischemic stroke for more than 6 months.
- •Imaging findings suggestive of ischemic stroke with functional deficits at initial diagnosis and enrollment.
- •Severe neurological impairment associated with the diagnosis of ischemic stroke that resulted in the subject needing assistance to walk or not being able to perform general daily activities independently.
- •No substantial improvement in neurologic or functional deficits for the 2 months prior to enrollment.
- •NIHSS score between 6-
- •Life expectancy longer than 12 months.
- •Prior to treatment, the patient received standard medical care for secondary prevention of ischemic stroke, including but not limited to appropriate blood pressure and cholesterol control measures, use of antiplatelet agents or anticoagulants (except when prohibited).
- •Understand and provide signed informed consent, or have a designated legal guardian or spouse make such decision voluntarily on behalf of the subject.
- •Expected that the patient will receive standard medical care for secondary prevention of ischemic stroke and participate in all planned safe follow-up visits reasonably.
- •Organ function as defined by the following criteria:
- •AST ≤ 2.5×ULN ALT ≤ 2.5×ULN TSB ≤1.5×ULN PT ≤1.25×ULN and PTT ≤1.25×ULN in subjects who did not receive antithrombotic therapy Serum albumin ≥ 3.0g/dL ANC ≥ 1,500/μL Platelets ≥ 150,000/μL Hemoglobin ≥ 9.0g/dL Serum creatinine ≤ 1.5×ULN Serum amylase or lipase ≤ 1.0×ULN
排除标准
- •History of epilepsy.
- •History of cancer.
- •History of brain trauma and brain tumor.
- •Positive for hepatitis B surface antigen, E antigen, E antibody, core antibody, hepatitis C, HIV or RPR.
- •Myocardial infarction occurred within six months of study entry.
- •Any other medical problems of clinical significance, abnormal mental or test results that the investigator or sponsor determined participating in the study pose a safety risk to the subject.
- •Imaging findings suggestive of subarachnoid hemorrhage or intracerebral hemorrhage in the past 12 months.
- •Participation in any study of experimental drug or device within 3 months.
- •Participation in other study related to stem cell-therapy.
- •History of drug or alcohol abuse within 1 year.
- •Pregnant, lactating or planning to become pregnant during the trial.
- •Allergic to cattle or pork products.
研究组 & 干预措施
Experimental: it-hMSC
Single intravenous infusion of 0.5×10^6, 1×10^6, 2×10^6 it-hMSC/kg
干预措施: it-hMSC (Drug)
Placebo-controlled: Placebo
Single intravenous infusion of 1 ml/kg placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of adverse events assessed by CTCAE V5.0 during the twelve-month study period after it-hMSC infusion.
时间窗: 12 months
次要结局
- Modified Rankin Scale(month 1, month 3, month 6, month 9, month 12)
- National Institute of Health stroke scale(month 1, month 3, month 6, month 9, month 12)
- Mini-mental State Examination(month 1, month 3, month 6, month 9, month 12)
- Barthel Index(month 1, month 3, month 6, month 9, month 12)
- Geriatric Depression Scale(month 1, month 3, month 6, month 9, month 12)