Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Ischemic Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- The incidence of major Serious Adverse Events (SAE)
研究概览
简要总结
The purpose of this clinical study is to evaluate the feasibility, safety and efficacy of intramyocardial injection of human induce pluripotent stem cell-derived cardiomyocytes (HiCM-188) during coronary artery bypass grafting (CABG) surgery in patients with severe chronic ischemic heart failure.
详细描述
This is a single center, open-label, three-group dose-escalation (phase I) study followed by dose-extension (phase IIa) study in up to 36 severe ischemic heart failure patients. It is estimated that up to 18 phase I patients will be received HiCM-188 intramyocardial injection during CABG surgery. The maximum number of subjects after dose escalation and dose extension studies in each dose group is 12. All the subjects need take immunosuppressant after transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥18 years
- •Willingness and ability to give written informed consent
- •Nuclide-myocardial metabolic perfusion imaging or Magnetic Resonance Imaging (MRI) revealed infarcted myocardium in the left anterior descending branch (LAD) coronary artery supply area
- •LVEF<50% as assessed by Echocardiography or LVEF≤40% as assessed by MRI
- •Patients have indications for Coronary Artery Bypass Grafting
排除标准
- •Presence of a pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy device (CRT)
- •Diagnosed with malignancy within 5 years
- •Autoimmune disease
- •Recipients of organ transplant.
- •Patients undergoing other surgical operations (excluding resection of ventricular aneurysm and left atrial appendage excision/occlusion).
- •Severe ventricular arrhythmia
- •Contraindication to CABG surgery
- •Contraindication to cardiac MRI or PET/CT scan.
- •Contraindication to immunosuppressants
- •Participation in another clinical trial within 3 months prior to screening
- •Pregnancy, lactation, or a positive serum pregnancy test
- •Any other condition considered by the investigator to be inappropriate for inclusion in this clinical trial
研究组 & 干预措施
HiCM-188 Low dose therapy
Intramyocardial injection of HiCM-188 (50 million) during CABG surgery.
干预措施: HiCM-188 therapy (Drug)
HiCM-188 Medium dose therapy
Intramyocardial injection of HiCM-188 (150 million) during CABG surgery.
干预措施: HiCM-188 therapy (Drug)
HiCM-188 High dose therapy
Intramyocardial injection of HiCM-188 (450 million) during CABG surgery.
干预措施: HiCM-188 therapy (Drug)
结局指标
主要结局
The incidence of major Serious Adverse Events (SAE)
时间窗: Within the first month after surgery
The incidence of major Serious Adverse Events (SAE) within the first month after surgery, including pericardial tamponade, nonfatal myocardial infarction, stroke, and all-cause death
次要结局
- Left ventricular geometry as assessed by cardiac magnetic resonance imaging (MRI)(Baseline, 6 and 12 months after surgery)
- Size of myocardial infarction as assessed by MRI(Baseline, 6 and 12 months after surgery)
- Cardiac output (CO) as assessed by MRI(Baseline, 6 and 12 months after surgery)
- Fractional shortening (FS) as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- Myocardial viability as assessed by SPECT(Baseline, 6 and 12 months after surgery)
- NT-proBNP Levels(Baseline, 6 and 12 months after surgery)
- New York Heart Association (NYHA) functional classification(Baseline, 6 and 12 months after surgery)
- Changes of Quality of Life(QOL) as assessed by 36-Item Short Form Survey (SF-36)(Baseline, 6 and 12 months after surgery)
- The incidence of tumor(12 months after surgery)
- Ventricular wall motion as assessed by MRI(Baseline, 6 and 12 months after surgery)
- Left ventricular ejection fraction as assessed by MRI(Baseline, 6 and 12 months after surgery)
- Cardiac Volumes as assessed by MRI(Baseline, 6 and 12 months after surgery)
- Left ventricular dimensions as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- Cardiac Volumes as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- 6-minute walking distance(Baseline, 6 and 12 months after surgery)
- Left ventricular ejection fraction (LVEF) as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- Mitral valve inflow spectrum(E/A) as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- Myocardial blood flow as assessed by SPECT(Baseline, 6 and 12 months after surgery)
- Changes of Quality of Life (QoL) as assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ)(Baseline, 6 and 12 months after surgery)
- Longitudinal strain as assessed by Echocardiography(Baseline, 6 and 12 months after surgery)
- Grade 4 or above arrhythmias Related to HiCM-188 Cell Therapy(Within the first month after surgery)
- End-diastolic myocardial mass as assessed by MRI(Baseline, 6 and 12 months after surgery)