Ad-HGF Treatment for Myocardial Infarction

Study Overview
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Brief Summary
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This will be the first clinical trial use Ad-HGF gene for the treatment of myocardial infarction disease.

Official Title
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Adenovirus Carrying Hepatocyte Growth Factor (Ad-HGF) Treatment for Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Ad-HGF
* Other: 0.9% NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18-80 years of age Clinical diagnosis of anterior ST-segment elevation myocardial infarction (STEMI) within the last 30 days, with any one of the following 12-lead electrocardiographic changes: a) Greater than or equal to 2 mm ST-segment elevation) in 2 adjacent electrocardiographic precordial leads b) A new left bundle branch block AND and an increase in cardiospecific enzymes >3x CK, or increase in troponin compared to institution laboratory normal ranges Successful PCI with stent implantation to infarct-related artery within the last 30 days; defined as residual stenosis no greater than 30%, Thrombolysis In Myocardial Infarction (TIMI) flow of at least 2 and a reference diameter of at least > 2mm Is considered hemodynamically stable at time of enrollment and immediately prior to Ad-HGF delivery Screening LVEF for the first 12 enrolled participants, must be no greater than 40% by echocardiography (determined by Simpson's method) performed at least 2 days after revascularization procedure. Subsequent participants enrolled in the trial, must have an LVEF no greater than 45%. (All screening echos done within the first 4 days post percutaneous coronary intervention (PCI) must be repeated either by echocardiography or MRI prior to Ad-HGF delivery to ensure that the variability does not exceed 10%) In the case of a previous myocardial infarction, documented LVEF must be 50% or greater Female participants must be surgically sterile, post-menopausal, have documented infertility, or are of child-bearing potential wih laboratory confirmation of non-pregnant state Provided written informed consent and is willing to comply with study follow-up visits Exclusion Criteria: Significant unprotected left main disease (stenosis of 50% or greater)on diagnostic angiography An increase in LVEF by greater that 10% from initial LVEF evaluation for repeat assessments The presence of significant coronary lesions, other than the index lesion of the infarction related artery A history of significant ventricular arrhythmia not related to index STEMI A history of cerebro-vascular accident or transient ischemic attack within 6 months of enrollment Inability to undergo apheresis procedure(i.e.: poor venous access, laboratory abnormalities A history of uncorrected significant valvular heart disease A history of left ventricular dysfunction prior to index STEMI A history of human immunodeficiency virus (HIV)or hepatitis B or C infection A history of malignancy within 5 years (Except for low-grade and fully resolved non-melanoma skin cancer) A history of allergy to gentamycin or amphotericin A history of non-compliance Active inflammatory autoimmune disease requiring chronic immunosuppressive therapy Creatinine clearance <60 by Cockcroft-Gault Calculator Confirmed pregnant or lactating Is enrolled in a current investigational drug or device trial Participant has received cell or gene therapy in past The presence of any significant co-morbidities that, in the investigator's opinion, would preclude the participant from taking part in the trial Inability to provide informed consent and comply with the follow-up visit schedule

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>Single dose of Ad-HGF given by investigator via intracoronary injection into infarct-related artery | Drug: Ad-HGF<br> <br> |
| Sham Comparator: control group<br>0.9% sodium chloride (NaCl) injection of same volume given by investigator via intracoronary injection into infarct-related artery | Other: 0.9% NaCl<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of cardiac left ventricular ejection fraction (LVEF, %) | the difference of LVEF before and after treatment between groups. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Measures (SF-36) | Participants will complete SF-36 to measure quality of life at baseline, 3 and 6 months. | Baseline to 6 months | 
| Activity Status (DASI) | Participants will complete DASI questionnaires to measure activity status at baseline, 3 and 6 months. | Baseline to 6 months | 
| changes of creatinine kinase (CK, U/L) within 24 hours post delivery. | the difference of creatinine kinase (CK, U/L) before and after delivery within 24 hours. | Baseline to 24 hours post delivery. | 
| changes of troponin (μg/L) within 24 hours post delivery. | the difference of troponin (μg/L) before and after delivery within 24 hours | Baseline to 24 hours post delivery. | 
| number of participants with evidence of any systemic embolization within 1 week post delivery. | number of participants with evidence of any systemic embolization during the hospitalization period post delivery. | Baseline to 1 week post delivery. | 
| number of participants with clinically significant changes in ECG than before | number of participants with clinically significant changes in ECG than before | Baseline to 6 months | 
| number of participants with major acute cardiac events (cardiac death and myocardial infarction) during follow-up | number of participants with major acute cardiac events (cardiac death and myocardial infarction) during follow-up | Baseline to 6 months | 
| number of participants with revascularization procedures during follow-up | number of participants with revascularization procedures during follow-up | Baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HGF,myocardial infarction