Safety and Efficacy Study of Gene Therapy for Acute Myocardial Infarction in Korea
Ischemic Heart Disease, Acute Myocardial Infarction
About this trial
This is an interventional treatment trial for Ischemic Heart Disease focused on measuring gene therapy
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 19 years to ≤ 75 years
- Patients who underwent percutaneous coronary intervention (PCI) for the anterior wall infarction of left ventricle and had the elapsed time of 30 ± 2 days from the PCI, regardless of success or failure of myocardial revascularization in the anterior wall
- Patients with > 20% to ≤ 45% of left ventricular ejection fraction via trans-thoracic echocardiography within 7 days prior to the study drug or placebo injection
- Left ventricular wall thickness ≥ 8 mm via trans-thoracic echocardiography (however, the subject shall be included if 50% or greater of the left ventricular anterior wall is ≥8mm or injection site other than the left ventricular anterior wall is ≥ 8mm.)
- If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study; if male, using barrier method of birth control during study
- Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures.
Exclusion Criteria:
- Severe systolic heart failure, NYHA Class III or IV
- New York Heart Association (NYHA) functional class IV
- History of recurrent ventricular tachycardia or cariogenic shock following PCI
- Stroke or transient ischemic attack (TIA) within 180 days
- Uncontrolled hypertension defined as systolic blood pressure ≥ 180 mmHg or diastolic ≥ 110 mmHg at screening and/or on the day of study drug or placebo injection
- Sustained ventricular tachyarrhythmia or recurrent ventricular tachycardia
- Implantation of automatic implantable cardioverter defibrillator (AICD)
- On extracorporeal membrane oxygenator (ECMO)
- History of ventricular fibrillation after PCI
- Permanent pacemaker implantation (temporary pacemaker may be enrolled)
- Subjects with aortic stenosis of moderate or greater degree, or with prosthetic aortic valve who may not be appropriate to use the C-CATHez® catheter due to the risk of injury during the interventional procedure through the valve
- Atherosclerotic or other disease of the aorto-iliac system that would impede the safe passage of the C-CATHez®
- Subjects with any serious comorbidities that the investigators deemed to be inappropriate to be enrolled
- Patients with a recent history (< 5 years) of, or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings
- Elevated prostate-specific antigen (PSA) despite not having prostate cancer history
- Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination Diagnosis of proliferative retinopathy or conditions that preclude standard ophthalmologic examination
- Subjects currently receiving immunosuppressive medications, chemotherapy, or radiation therapy
- Active infectious disease and/or positive Human Immunodeficiency Virus (HIV) or Human T-Cell lymphotropic viruses (HTLV) at screening
- Active Hepatitis B or C infection as determined by Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (Immunoglobulin G and Immunoglobulin M; HBcAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV) at screening
Specific laboratory values at screening including
- Hemoglobin ≤ 9.0 g/dL, white blood cell (WBC) < 3,000 cells/μl, platelet count < 75,000/mm3
- Creatinine > 2.0 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
- Any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary
- Subjects requiring > 100 mg daily of acetylsalicylic acid (ASA); subjects may be enrolled if willing/able to switch to ≤ 100 mg daily of ASA or to another medication
- Subjects regularly taking cyclooxygenase (COX)-2 inhibiting drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (except inhaled steroids); subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs for the duration of the study, and also if the subject is temporarily taking NSAID (non-steroidal anti-inflammatory drug) temporarily (≤ 7 days)
- Patients that have undergone enhanced external pulsation (EECP) treatment within the last 6 months
- Pregnancy or lactation
- Severe comorbidity associated with a reduction of life expectancy of less than 1 year
- Exposure to any previous experimental angiogenic therapy and/or myocardial laser therapy; or therapy with another investigational drug within 180 days of enrollment or participation in any concurrent study that may confound the results of this study
- Major psychiatric disorder in the past 6 months
- Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or who in the opinion of the investigator are not suitable to participate
- Deemed to be in unsuitable condition by the study investigator
Sites / Locations
- GangNeung Asan HospitalRecruiting
- Chonnam National University HospitalRecruiting
- Ewha Womans University Medical CenterRecruiting
- KyungHee University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Stage 1-Low dose VM202RY
Stage 1-Middle dose VM202RY
Stage 1-High dose VM202RY
Stage 2-Placebo
Stage 2-Low dose VM202RY
Stage 2-High dose VM202RY
Patients in this group will receive total 1mg of VM202RY. (4 sites of 0.25mg/0.5 mL VM202RY)
Patients in this group will receive total 2mg of VM202RY. (8 sites of 0.25mg/0.5 mL VM202RY)
Patients in this group will receive total 3mg of VM202RY. (12 sites of 0.25mg/0.5 mL VM202RY)
Patients in this group will receive 6mL of VM202RY vehicle. (12 sites of 0.5mL 0.9% NaCl, 1.1% sucrose)
Patients in this group will receive total 6mL of VM202RY and VM202RY vehicle. (The dose of VM202RY can be one of the three candidate-0.5mg VM202RY/1mg VM202RY/1.5mg VM202RY based on the tolerated dose result from Stage 1.)
Patients in this group will receive total 6mL of VM202RY and VM202RY vehicle. (The dose of VM202RY can be one of the three candidate-1mg VM202RY/2mg VM202RY/3mg VM202RY based on the tolerated dose result from Stage 1.)