The purpose of this study is to evaluate the safety and clinical efficacy of VM202RY injected via transendocardial route using C-Cathez® catheter (Celyad, S.A., Belgium) in subjects with AMI. * Stage 1: Evaluation of safety and tolerability of VM202RY injection * Stage 2: Evaluation of safety and efficacy of VM202RY injection
Ischemic heart disease, a condition in which narrowed or blocked coronary arteries lead to ischemia in myocardium, is a group of disease that include: angina and myocardial infarction. Acute myocardial infarction (AMI) predicts rapid progression of necrosis. AMI is a serious health condition that it's mortality rate is about 30% and also more likely to have a higher incidence of cardiac dysrhythmia or ventricular aneurysm. Therapeutic angiogenesis is promising approach for the treatment of cardiovascular disease. 66 to 75% of coronary artery disease patients have insufficient coronary collaterals and 30% of myocardial infarction patients display inadequate myocardial perfusion although there are procedures like percutaneous coronary intervention or coronary artery bypass graft surgery. In phase I study for ischemic heart disease, VM202RY appeared to have improved regional myocardial perfusion and wall thickness of the diastolic and systolic phases in the injected region. These results suggest that VM202RY improves the myocardial perfusion and inhibits cardiac remodeling in ischemic heart disease patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Day 0: 1mg of VM202RY (4 sites of 0.25mg/0.5mL VM202RY)
Day 0: 2mg of VM202RY (8 sites of 0.25mg/0.5mL VM202RY)
Day 0: 3mg of VM202RY (12 sites of 0.25mg/0.5mL VM202RY)
GangNeung Asan Hospital
Gangneung, South Korea
Chonnam National University Hospital
Gwangju, South Korea
Ewha Womans University Medical Center
Seoul, South Korea
KyungHee University Medical Center
Seoul, South Korea
Stage 1: MTD (maximum tolerated dose)
• MTD is defined as the dose level below the dose at which ≥ 33% of participants experienced DLT (dose limiting toxicity). The DLT assessment will be conducted on day 14. Toxicities more severe than grade 3 on the WHO toxicity scale will be designated as DLT. The dose where severe adverse events occur according to the Spilker classification will also be designated as DLT. The assessment will be conducted from the lowest dose to higher doses incrementally. MTD will be measured in milligrams (mg).
Time frame: 6 months
Stage 2: LVEF (left ventricular ejection fraction) measured by cardiac MRI
• The change in LVEF measured by cardiac MRI in VM202RY and placebo will be compared at 6 months after the treatment of VM202RY or Placebo by transendocardial injections using C-CATHez® catheter. LVEF will be measured in percentage (%).
Time frame: 6 months
Change in left ventricular diameter (cardiac MRI)
The change in diameter of left ventricle will be measured in millimeters (mm), at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in left ventricular diameter (TTE)
The change in diameter of left ventricle will be measured in millimeters (mm), at months 3 and 6 using TTE (transthoracic echocardiogram).
Time frame: 3 and 6 months
Change in left ventricular volume (cardiac MRI)
The change in volume of left ventricle will be measured in milliliters (mL), at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in left ventricular volume (TTE)
The change in volume of left ventricle will be measured in milliliters (mL), at months 3 and 6 using TTE.
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Day 0: 6mL of VM202RY vehicle (12 sites of 0.5mL 1.1% sucrose/0.9% NaCl)
Day 0: 6mL of VM202RY and VM202RY vehicle (total 12 site injections, low dose candidate-0.5mg VM202RY, 1mg VM202RY, 1.5mg VM202RY)
Day 0: 6mL of VM202RY and VM202RY vehicle (total 12 site injections, high dose candidate-1mg VM202RY, 2mg VM202RY, 3mg VM202RY)
Day 0 (Stage 1-Low dose VM202RY): 1mg of VM202RY (4 sites of 0.25mg/0.5mL VM202RY) Day 0 (Stage 1-Middle dose VM202RY): 2mg of VM202RY (8 sites of 0.25mg/0.5mL VM202RY) Day 0 (Stage 1-High dose VM202RY): 3mg of VM202RY (12 sites of 0.25mg/0.5mL VM202RY) Day 0 (Stage 2-Placebo): 6mL of VM202RY vehicle (12 sites of 0.5mL 1.1% sucrose/0.9% NaCl) Day 0 (Stage 2-Low dose VM202RY): 6mL of VM202RY and VM202RY vehicle (total 12 site injections, low dose candidate-0.5mg VM202RY, 1mg VM202RY, 1.5mg VM202RY) Day 0 (Stage 2-High dose VM202RY): 6mL of VM202RY and VM202RY vehicle (total 12 site injections, high dose candidate-1mg VM202RY, 2mg VM202RY, 3mg VM202RY)
Time frame: 3 and 6 months
Change in cardiac output (cardiac MRI)
The change in cardiac output will be measured in liters per minute (L/min), at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in cardiac output (TTE)
The change in cardiac output will be measured in liters per minute (L/min), at months 3 and 6 using TTE.
Time frame: 3 and 6 months
Change in LVEF (cardiac MRI)
The change in left ventricular ejection fraction will be measured in percentage (%), at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in LVEF (TTE)
The change in left ventricular ejection fraction will be measured in percentage (%), at months 3 and 6 using TTE.
Time frame: 3 and 6 months
Change in wall motion score index (cardiac MRI)
The wall motion score index will be measured at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in wall motion score index (TTE)
The wall motion score index will be measured at months 3 and 6 using TTE.
Time frame: 3 and 6 months
Change in myocardial wall thickness (cardiac MRI)
The change in myocardial wall thickness of the investigational-product or placebo injected area will be measured in millimeters (mm) at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in extent of late enhancement of gadolinium (cardiac MRI)
The change in extent of late enhancement of gadolinium will be measured at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in rest perfusion (cardiac MRI)
The change in rest perfusion will be measured in percentage (%) at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in rest perfusion (myocardial SPECT)
The change in rest perfusion will be measured in percentage (%) at months 3 and 6 using myocardial SPECT.
Time frame: 3 and 6 months
Change in stress perfusion (cardiac MRI)
The change in stress perfusion will be measured in percentage (%) at months 3 and 6 using cardiac MRI.
Time frame: 3 and 6 months
Change in stress perfusion (myocardial SPECT)
The change in stress perfusion will be measured in percentage (%) at months 3 and 6 using myocardial SPECT.
Time frame: 3 and 6 months