Safety Study of Gene Therapy for Ischemic Heart Disease in Korea

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety of VM202RY direct injection into the cardiac muscles of the coronary artery territory where complete revascularization could not be done even through Coronary Artery Bypass Graft.

Detailed Description
-----------------
All the patients expected to undergo Coronary Artery Bypass Graft 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). VM202RY 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. VM202RY will be administered to Group1 (0.5mg), Group 2 (1mg) and Group 3 (2mg) 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.

Official Title
-----------------
Open-label, Dose-escalation, Phase 1 Trial to Evaluate the Safety of VM202RY Gene Medicine Injected Into Myocardial Territory With Incomplete Revascularization During Coronary Artery Bypass Graft in Patients With Ischemic Heart Disease

Conditions
-----------------
Ischemic Heart Disease

Intervention / Treatment
-----------------
* Biological: VM202RY
* Biological: VM202RY
* Biological: VM202RY


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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 premenopausal 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

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I<br>0.5mg/1mL of VM202RY was intramuscularly injected into 4 sites | Biological: VM202RY<br>* 0.5mg intramuscular injection<br>|
| Experimental: Cohort II<br>1mg/2mL of VM202RY was intramuscularly injected into 8 sites | Biological: VM202RY<br>* 1mg intramuscular injection<br>|
| Experimental: Cohort III<br>2mg/4mL of VM202RY was intramuscularly injected into 8 sites | Biological: VM202RY<br>* 2mg intramuscular injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events |  | 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cardiac function, size of viable myocardium and myocardial ischemic area |  | Day0, 12weeks, 24weeks |