Open-label, Non-comparative, Dose-escalation, Single-center, Phase 1 Trial to Evaluate the Safety of VM202RY Gene Medicine Injected Into Cardiac Muscle of Incompletely Revascularized Area After CABG in Patients With Ischemic Heart Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- The Incidence of Adverse Events - Total Adverse Events (AE)
研究概览
简要总结
The purpose of this study is to evaluate the safety of VM202 (Engensis) direct injection into the cardiac muscles of the coronary artery territory where complete revascularization could not be done even through Coronary Artery Bypass Graft (CABG).
详细描述
All the patients expected to undergo Coronary Artery Bypass Graft (CABG) will screen for the participation in the clinical study. Subjects who signed the informed consent will receive all the screening tests within 21 days before surgery (Day 0). VM202 (Engensis) will be injected into 4 sites or 8 sites on the coronary artery where complete revascularization was not done since vascular anastomosis could not be performed due to the bad vascular condition during surgery. VM202 (Engensis) will be administered to Group1 (0.5 mg), Group 2 (1 mg) and Group 3 (2 mg) at different concentrations. Subjects will be scheduled to get inpatient treatment during the gene therapy period (7 days) and follow-up tests at Week 2, 4, 8, 12 and 24 based on surgery day (Day 0). Adverse events and concomitant drugs will be checked.
Safety: Evaluated for 6 months after the administration of VM202 (Engensis).
- Dose-Limiting Toxicity (DLT)
- Tolerated Dose (TD)
- Adverse events, vital signs, physical examination and laboratory test values
- Major Adverse Cardiac Event (MACE) - cardiac death, myocardial infarction, ventricular arrhythmia requiring treatment, or hospitalization for revascularization of target blood vessels)
- Safety of VM202 intramyocardial injection: persistent hemorrhage, arrhythmia and other complications
Secondary endpoints
- Efficacy
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 19 and ≤ 75 years
- •Patients in whom decrease of myocardial perfusion in coronary artery territories (rest perfusion - stress perfusion: ≥ 7%) was observed by myocardial SPECT
- •Patients judged to have possibly incomplete revascularization based on the observation of the coronary artery's internal diameter of ≤ 1 mm, diffuse atherosclerosis or severe calcification on coronary angiography, or patients judged to have some myocardial perfusion territories that could not be performed Coronary Artery Bypass Graft
- •Patients who or whose legal representative can write the informed consent before the initiation of the clinical study and comply with the requirements
排除标准
- •Patients with progressive or present heart failure
- •Patients with uncontrolled ventricular arrhythmia on electrocardiogram, or who have been treated for ventricular arrhythmia
- •Patients with current or history of malignant tumor
- •Patients with severe infectious disease
- •Patients with uncontrolled hematologic disorders
- •Patients requiring surgery for the accompanying valve diseases or left ventricular volume reduction surgery
- •Patients with current or history of proliferative retinopathy
- •Patients with remaining life of less than 1 year and severe accompanying diseases enough to die during the clinical follow-up period
- •Patients with history of drug or alcohol abuse within the recent 3 months
- •Women who are pregnant or breast feeding or postmenopausal women of childbearing age. However, women who underwent surgical sterilization including hysterectomy or bilateral tubal ligation can participate in this clinical trial. Even though they consent to the contraception, they cannot be enrolled.
- •Patients in inappropriate condition judged by investigators
- •Patients with cerebrovascular diseases (cerebral infarction, cerebral bleeding or transient ischemic attack that are currently occurring or occurred within 6 months)
- •Patients with idiopathic hypertension who are not controlled with drugs
- •Patients with severe hepatic disorders
- •Patients with severe renal disorders
- •Patients who underwent Coronary Artery Bypass Graft
- •Patients who underwent angioplasty within 1 year before their enrollment in the study
研究组 & 干预措施
Cohort II
1 mg/ 2 mL of VM202 was intramyocardially injected into 8 sites
干预措施: VM202-1.0 mg (Biological)
Cohort III
2 mg/ 4 mL of VM202 was intramyocardially injected into 8 sites
干预措施: VM202-2.0 mg (Biological)
Cohort I
0.5 mg/ 1 mL of VM202 was intramyocardially injected into 4 sites
干预措施: VM202-0.5 mg (Biological)
结局指标
主要结局
The Incidence of Adverse Events - Total Adverse Events (AE)
时间窗: 24 weeks
Subjects who have been administered the investigational drug will be included, regardless of protocol violations or adherence to visit schedules. This clinical trial is designed to evaluate safety over a 6-month period. Assessments Include: Adverse reactions, vital signs, physical exam, laboratory test results
The Severity of Adverse Events - Total Adverse Events by Severity
时间窗: 24 weeks
Subjects who have been administered the investigational drug will be included, regardless of protocol violations or adherence to visit schedules. This clinical trial is designed to evaluate safety over a 6-month period. Assessments Include: Adverse reactions, vital signs, physical exam, laboratory test results
次要结局
- Percentage of Change From Baseline/Screening in Left Ventricular Ejection Fraction Evaluated by Magnetic Resonance Imaging(Day 0, 12 weeks, 24 weeks)
- Percentage of Change From Baseline/Screening in Cardiac Function Evaluated by Echocardiography(Day 0, Day 7, 12 weeks, 24 weeks)
- Changes in Size of Viable Myocardium - End-Systolic Thickness(Day 0, 12 weeks, 24 weeks)
- Changes in Size of Viable Myocardium - End-Diastolic Thickness(Day 0, 12 weeks, 24 weeks)
- Changes in Myocardial Ischemic Area - Stress Condition(Day 0, 12 weeks, 24 weeks)
- Changes in Myocardial Ischemic Area - Resting Condition(Day 0, 12 weeks, 24 weeks)