Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure.

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo controlled Phase II study is designed to assess the safety and efficacy of using JVS-100 to treat heart failure.

Detailed Description
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90 subjects with ischemic cardiomyopathy will be randomized to receive a single dose of 15 or 30 mg of JVS-100 or matching placebo. Subjects will be randomized 1:1:1 to receive either placebo, 15 mg or 30 mg of JVS-100. Subjects will be monitored overnight for 18-24 hours post dose and have scheduled visits at 3 days post-injection for safety evaluations. All subjects will be scheduled for follow-up visits at approximately 30 days (1 month), 120 days (4 months), and 360 days (12 months) to assess safety and cardiac function.

Official Title
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A Phase II Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of a Single Dose of JVS-100 Administered by Endomyocardial Injection to Cohorts of Adults With Ischemic Heart Failure

Conditions
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Ischemic Heart Failure

Intervention / Treatment
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* Biological: JVS-100 15 mg dose Injection
* Biological: Placebo Injection
* Biological: JVS-100 30 mg dose injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign informed consent Greater than or equal to 18 years of age Subjects with impaired 6 minute hall walk distance Impaired quality of life as measured by Minnesota LWHF questionnaire Ischemic cardiomyopathy without an acute coronary syndrome within the last 6 months Residual well-demarcated region of LV systolic dysfunction defined as at least 3 consecutive segments of abnormal wall motion by echocardiography read at the echocardiography core laboratory LVEF ≤40% measured by echocardiography read at the echocardiography core laboratory Must meet wall thickness criteria Subject has an implanted, functional AICD Subjects with diabetes must have had an ophthalmologist exam within the last year showing no active proliferative retinopathy Subject receiving stable optimal pharmacological therapy defined as: ACE inhibitor and/or ARB, and Beta-blocker for 90 days with stable dose for 30 days unless contraindicated Diuretic in subjects with evidence of fluid retention ASA unless contraindicated Statin unless contraindicated Aldosterone antagonist per physician discretion Exclusion Criteria: Planned revascularization within 30 days following enrollment Estimated Glomerular Filtration Rate < 30 ml/min* Signs of acute heart failure within 24 hours of scheduled injection History of aortic valve regurgitation classified as moderate or severe Moderate/Severe aortic stenosis defined as AVA <1.5 cm2 Note: Patient should not be excluded if the patient's medical records document that within the last 6 months the patient has either: no aortic stenosis mild aortic stenosis normal aortic valve normal aortic pressure gradient aortic pressure gradient < 20 mmHg Presence of an artificial aortic valve Subjects with aortic aneurysm >3.8 cm Mitral regurgitation defined as severe measured by echocardiography at the clinical site. Patients with planned mitral valve repair or replacement surgery Any patient with a history of cancer will be excluded unless: The cancer was limited to curable non-melanoma skin malignancies and/or The cancer was removed by a successful tumor resection, with or without radiation or chemotherapy treatment, 5 years or more prior to enrollment in this study without recurrence Subjects must have the following results on age appropriate cancer screenings: Subjects age 50 or older have had a Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) that was negative within the last year Women age 30 or older have had a PAP test that was negative within the last 3 years Women age 40 or older have had a mammogram that was negative within the last year Men above age 45 have had a Prostate-Specific Antigen (PSA) blood test and digital rectal examination (DRE) that was negative within the last year At the request of the site principal investigator, any subject with a non-negative result thought to be due to a non-cancer-related condition will be evaluated by the medical monitor for enrollment Exclusion Criteria (ctd): Subjects with persistent or chronic atrial fibrillation will be excluded unless: A stable, regular heart rate is maintained with a biventricular pacemaker A stable, regular heart rate is maintained with a univentricular pacemaker pacing less than or equal to 40% of the time Subjects with Biventricular pacing device implant within the last 3 months OR previously implanted Biventricular pacing device with programming planned to be reoptimized following enrollment in this trial Previous solid organ transplant Subjects with greater than 40% univentricular RV Pacing Subjects with uncontrolled diabetes defined as HbA1c >9.0% Inability to complete 6 minute walk or treadmill exercise test Participation in an experimental clinical trial within 30 days prior to enrollment Any subject who has been enrolled in a gene or stem cell therapy cardiac trial within the last year Life expectancy of less than 1 year Positive pregnancy test (serum βHCG) in women of childbearing potential and/or unwillingness to use contraceptives or limit sexual activity as described in Section 8.2.1 below Unwillingness of men capable of fathering a child to agree to use barrier contraception or limit sexual activity as described in Section 8.2.1 below Subjects who are breast feeding Subjects with a positive test results for hepatitis B/C and/or HIV Total Serum Bilirubin >4.0 mg/dl Aspartate aminotransferase (AST) > 120 IU/L Alanine aminotransferase (ALT) > 135 IU/L Alkaline phosphatase (ALP) >300 IU/L Clinically significant elevations in PT or PTT relative to laboratory norms Any subject with a known existing LV thrombus or has an LV thrombus detected during the screening period of this study. Subjects with Rutherford class 5 or 6 critical limb ischemia Subject with severe chronic obstructive pulmonary disease (COPD) Any subject requiring home oxygen use Subjects with a history of Systemic Lupus Erythematosus (SLE) flare History of drug or alcohol abuse within the last year A subject will be excluded if he/she is unfit for the trial based on the discretion of the site Principal Investigator

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Biological: Placebo Injection<br>* Intramyocardial Injection<br>|
| Experimental: 15 mg dose of JVS-100<br>15 mg dose of JVS-100 | Biological: JVS-100 15 mg dose Injection<br>* Intramyocardial Injection<br>|
| Experimental: 30 mg dose of JVS-100<br>30 mg dose of JVS-100 | Biological: JVS-100 30 mg dose injection<br>* Intramyocardial Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of JVS-100 injection on Six Minute Walk Distance (6MWD) at 4 month follow-up | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on 6 minute walk distance compared to placebo at 4 months post-dosing | 4 Months | 
| Impact of JVS-100 injection on Quality of Life at 4 month follow-up | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on quality of life measured by the Minnesota Living with Heart Failure Questionnaire compared to placebo at 4 months post-dosing | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of JVS-100 Injection on Quality of Life | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on quality of life measured by the Minnesota Living with Heart Failure Questionnaire compared to placebo at 12 months post-dosing | 12 Months | 
| Impact of JVS-100 Injection on NYHA class | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on NYHA class compared to placebo at 4 months post-dosing | 4 months | 
| Impact of JVS-100 Injection on LVEF | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on Left Ventricular Ejection Fraction as measured by echocardiography compared to placebo at 4 months post-dosing | 4 months | 
| Impact of JVS-100 Injection on Time to First Heart Failure Decompensation | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on the time to first heart failure decompensation compared to placebo | Up to 12 months | 
| Impact of JVS-100 Injection on Major Adverse Cardiac Events | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on the number of major adverse cardiac events (MACE) compared to placebo | Up to 12 months | 
| Impact of JVS-100 Injection on number of adverse events | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on the number of adverse events compared to placebo | Up to 12 months | 
| Impact of JVS-100 Injection on number of serious adverse events | To investigate the impact of single doses of JVS-100 (either 15 or 30 mg) delivered via endomyocardial injection through the BioCardia Helical Infusion catheter on the number of serious adverse events compared to placebo | Up to 12 months |