Safety Study of Gene Therapy for Ischemic Heart Disease in Korea (Engensis)

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

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).

Study Overview

• Status: Completed
• Conditions: Ischemic Heart Disease
• Intervention / Treatment: Biological: VM202-0.5 mg; Biological: VM202-1.0 mg; Biological: VM202-2.0 mg

Detailed Description

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
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort I; 0.5 mg/ 1 mL of VM202 was intramyocardially injected into 4 sites	Biological: VM202-0.5 mg; 0.5 mg intramyocardial injection
Experimental: Cohort II; 1 mg/ 2 mL of VM202 was intramyocardially injected into 8 sites	Biological: VM202-1.0 mg; 1 mg intramyocardial injection
Experimental: Cohort III; 2 mg/ 4 mL of VM202 was intramyocardially injected into 8 sites	Biological: VM202-2.0 mg; 2 mg intramyocardial injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 weeks
The Severity of Adverse Events - Total Adverse Events by Severity	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	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Day 0, Day 7, 12 weeks, 24 weeks
Changes in Size of Viable Myocardium - End-Systolic Thickness	The size of the viable myocardium was evaluated based on the myocardium thickness at the site of intramyocardial gene injection by Magnetic Resonance Imaging - End-Systolic Thickness. Using cardiac MRI, the myocardial thickness at the gene injection site, the extent of late gadolinium enhancement, and local wall motion strength will be evaluated. Differences between groups before and after VM202RY administration will be tested using the Kruskal-Wallis test.	Day 0, 12 weeks, 24 weeks
Changes in Size of Viable Myocardium - End-Diastolic Thickness	The size of the viable myocardium was evaluated based on the myocardium thickness at the site of intramyocardial gene injection by Magnetic Resonance Imaging - End-Diastolic Thickness. Using cardiac MRI, the myocardial thickness at the gene injection site, the extent of late gadolinium enhancement, and local wall motion strength will be evaluated. Differences between groups before and after VM202RY administration will be tested using the Kruskal-Wallis test.	Day 0, 12 weeks, 24 weeks
Changes in Myocardial Ischemic Area - Stress Condition	Changes in Myocardial Ischemic Area evaluated by 99mTc Sestamibi Methoxyl Isobutyl Isonitrile Single Photon Emission Computed Tomography (SPECT) based on Percentage of perfusion volume - Stress Condition	Day 0, 12 weeks, 24 weeks
Changes in Myocardial Ischemic Area - Resting Condition	Changes in Myocardial Ischemic Area evaluated by 99mTc Sestamibi Methoxyl Isobutyl Isonitrile Single Photon Emission Computed Tomography (SPECT) based on Percentage of perfusion volume - Resting Condition	Day 0, 12 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: Helixmith Co., Ltd.
• Investigators: Principal Investigator: Gibong Kim, MD, PhD, Seoul National University Hospital

Publications and helpful links

General Publications

• Kim JS, Hwang HY, Cho KR, Park EA, Lee W, Paeng JC, Lee DS, Kim HK, Sohn DW, Kim KB. Intramyocardial transfer of hepatocyte growth factor as an adjunct to CABG: phase I clinical study. Gene Ther. 2013 Jul;20(7):717-22. doi: 10.1038/gt.2012.87. Epub 2012 Nov 15.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: August 21, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (Estimated): August 24, 2011

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Coronary Artery Bypass Graft; VM202; Engensis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia
• Other Study ID Numbers: VM202RY-VM01