Safety Study of Gene Therapy for Ischemic Heart Disease i... | NCT01422772

NCT01422772

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Oversight Module

Description Module

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).

Dose-Limiting Toxicity (DLT)
Tolerated Dose (TD)
Adverse events, vital signs, physical examination and laboratory test values
Major Adverse Cardiac Event (MACE) - cardiac death, myocardial infarction, ventricular arrhythmia requiring treatment, or hospitalization for revascularization of target blood vessels)
Safety of VM202 intramyocardial injection: persistent hemorrhage, arrhythmia and other complications

Secondary endpoints

- Efficacy

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)
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)
Changes in myocardial ischemic area: By myocardial SPECT (blood flow changes at intramyocardial gene injection site from resting to stress condition)

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort I	Experimental	0.5 mg/ 1 mL of VM202 was intramyocardially injected into 4 sites	Biological: VM202-0.5 mg
Cohort II	Experimental	1 mg/ 2 mL of VM202 was intramyocardially injected into 8 sites	Biological: VM202-1.0 mg
Cohort III	Experimental	2 mg/ 4 mL of VM202 was intramyocardially injected into 8 sites	Biological: VM202-2.0 mg

Name	Type	Description	Arm Group Labels	Other Names
VM202-0.5 mg	Biological	0.5 mg intramyocardial injection	Cohort I

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

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 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.
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

Name	Affiliation	Role
Gibong Kim, MD, PhD	Seoul National University Hospital	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
23151518	Background	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.

Arm/Group Information

ID	Title	Description
FG000	Group 1 - 0.5 mg/1 mL	VM202 (Engensis) 0.5 mg/1 mL was intramyocardially injected into 4 sites 0.125 mg/0.25 mL/injection point) of the incompletely revascularized area after Coronary Artery Bypass Graft.
FG001	Group 2 - 1.0 mg/2 mL	VM202 (Engensis) 1 mg/2 mL was intramyocardially injected into 8 sites (0.125 mg/0.25 mL/injection point) of the incompletely revascularized area after Coronary Artery Bypass Graft.
FG002	Group 3 - 2 mg/4 mL	VM202 (Engensis) 2 mg/4 mL was intramyocardially injected into 8 sites (0.25 mg/0.5 mL/injection point) of the incompletely revascularized area after Coronary Artery Bypass Graft.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Group 1 - VM202 - 0.5 mg/ 1mL	VM202RY 0.5 mg/ 1 mL was intramyocardially injected into 4 sites (0.125 mg/0.25 mL/injection point) of the incompletely revascularized area after Coronary Artery Bypass Graft.
BG001	Group 2 - VM202 - 1.0 mg/2 mL

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Total Number of Adverse Events (ITT Safety)

Posted

Number

Total AEs

24 weeks

Total AEs

ID	Title	Description
OG000	Group 1 - 0.5 mg/1 mL	VM202 (Engensis) 0.5 mg/1 mL was intramyocardially injected into 4 sites 0.125 mg/0.25 mL/injection point) of the incompletely revascularized area after Coronary Artery Bypass Graft.
OG001	Group 2 - 1.0 mg/2 mL

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1 - VM202 - 0.5 mg/ 1mL	VM202RY 0.5mg/1mL was intramyocardially injected into 4 sites

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Worsening Spinal Stenosis	Musculoskeletal and connective tissue disorders	Medra 13.0	Systematic Assessment	Musculoskeletal and connective tissue disorders spinal column stenosis

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases