Safety Study of Gene Therapy for Ischemic Heart Disease in Korea

Helixmith Co., Ltd.9 enrolled

Overview

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).

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). 1. Dose-Limiting Toxicity (DLT) 2. Tolerated Dose (TD) 3. Adverse events, vital signs, physical examination and laboratory test values 4. Major Adverse Cardiac Event (MACE) - cardiac death, myocardial infarction, ventricular arrhythmia requiring treatment, or hospitalization for revascularization of target blood vessels) 5. Safety of VM202 intramyocardial injection: persistent hemorrhage, arrhythmia and other complications Secondary endpoints \- Efficacy 1. Changes in cardiac function: Left ventricular ejection fraction and cardiac function in the local region by cardiac MRI (Magnetic Resonance Imaging), myocardial SPECT (99 mTc Sestamibi Methoxyl Isobutyl Isonitrile Single Photon Emission Computed Tomography) and Trans Thoracic echocardiography (TTE) 2. Size of viable myocardium: By cardiac MRI (myocardial thickness of intramyocardial gene injection site, gadolinium late contrast enhancement range and the exercise intensity of the local region) 3. Changes in myocardial ischemic area: By myocardial SPECT (blood flow changes at intramyocardial gene injection site from resting to stress condition)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ischemic Heart Disease

Interventions

VM202-0.5 mgBIOLOGICAL

0.5 mg intramyocardial injection

VM202-1.0 mgBIOLOGICAL

1 mg intramyocardial injection

VM202-2.0 mgBIOLOGICAL

2 mg intramyocardial injection

Eligibility

Sex: ALLMin age: 19 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients aged ≥ 19 and ≤ 75 years 2. Patients in whom decrease of myocardial perfusion in coronary artery territories (rest perfusion - stress perfusion: ≥ 7%) was observed by myocardial SPECT 3. 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 4. 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: 1. Patients with progressive or present heart failure 2. Patients with uncontrolled ventricular arrhythmia on electrocardiogram, or who have been treated for ventricular arrhythmia 3. Patients with current or history of malignant tumor 4. Patients with severe infectious disease 5. Patients with uncontrolled hematologic disorders 6. Patients requiring surgery for the accompanying valve diseases or left ventricular volume reduction surgery 7. Patients with current or history of proliferative retinopathy 8. Patients with remaining life of less than 1 year and severe accompanying diseases enough to die during the clinical follow-up period 9. Patients with history of drug or alcohol abuse within the recent 3 months 10. 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. 11. Patients in inappropriate condition judged by investigators 12. Patients with cerebrovascular diseases (cerebral infarction, cerebral bleeding or transient ischemic attack that are currently occurring or occurred within 6 months) 13. Patients with idiopathic hypertension who are not controlled with drugs 14. Patients with severe hepatic disorders 15. Patients with severe renal disorders 16. Patients who underwent Coronary Artery Bypass Graft 17. Patients who underwent angioplasty within 1 year before their enrollment in the study

Locations (1)

Seoul National University Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

The Incidence of Adverse Events - Total Adverse Events (AE)

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

Time frame: 24 weeks

The Severity of Adverse Events - Total Adverse Events by Severity

Time frame: 24 weeks

Secondary Outcomes

Percentage of Change From Baseline/Screening in Left Ventricular Ejection Fraction Evaluated by Magnetic Resonance Imaging

Changes in Percentage of Left Ventricular Ejection Fraction by Cardiac Magnetic Resonance Imaging (MRI). Cardiac MRI will be used to monitor for the development of intramyocardial hemangiomas. Analysis will follow the standard cardiac MRI protocols of the Department of Radiology at Seoul National University Hospital, using an appropriate segment model based on the patient's heart size. Parameters evaluated will include left ventricular volume (mL), wall motion index, myocardial thickness (mm), and LVEF (%). Comparisons will be made between baseline/screening and follow-up measurements for each patient, as well as between treatment groups.

Time frame: Day 0, 12 weeks, 24 weeks

Percentage of Change From Baseline/Screening in Cardiac Function Evaluated by Echocardiography

Changes from screening in cardiac function evaluated based on Percentage of Left Ventricular Ejection Fraction by cardiac Trans-thoracic Echocardiography (TTE). From transthoracic echocardiography, left ventricular diameter (mm), ejection fraction (%), and wall thickness (mL) will be measured and compared from Screening/Baseline to follow-up results after surgery. The Wall Motion Score Index will be calculated by dividing the myocardium into 16 segments and assigning a score to each area based on motion: \[1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic\]. The total score for the entire myocardium and the right coronary artery region will be averaged by the number of segments.

Data from ClinicalTrials.gov

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