Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure
Study to Evaluate the Safety and Efficacy of JVS-100 Administered to Adults With Ischemic Heart Failure
A phase I/II study to evaluate the safety and efficacy of JVS-100 administered by retrograde
 delivery to cohorts of adults with Ischemic Heart Failure.
72 subjects with ischemic cardiomyopathy. The Phase I portion (n=12 subjects) will be open
 label. In the first cohort, six subjects will receive a single dose of 30 mg of JVS-100 with
 a minimum of 3 days between each enrollment. After seven days following the enrollment of the
 last patient of cohort 1, a safety assessment by the DSMC will be performed. Upon DSMC
 approval, the second cohort of six subjects will receive a single dose of 45 mg of JVS-100
 with a minimum of 3 days between each enrollment. After seven days following the enrollment
 of the last patient of cohort 2, a safety assessment by the DSMC will be performed. Upon DSMC
 approval, up to 60 subjects will be randomized (1:1:1) to receive a single dose of 30 mg or
 45 mg of JVS-100 or matching placebo.
Inclusion Criteria:

 -  Willing and able to sign informed consent

 -  Greater than or equal to 18 years of age

 -  Poor quality of life as measured by the Minnesota Living with Heart Failure
 Questionnaire (MLWHFQ)

 -  Impaired 6 Minute Walk test

 -  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 less than or equal to 40% measured by echocardiography read at the
 echocardiography core laboratory

 -  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

 -  Subject must not have a permanent device placed in the coronary sinus at the time of
 enrollment *As defined as no more than 50% change in dose

 Exclusion Criteria:

 -  Planned revascularization within 30 days following enrollment

 -  Note: if an angiographic study has been performed within the last year and the
 subject is enrolled, the angiography study report should be included as part of
 the subject's file

 -  Estimated Glomerular Filtration Rate < 30 ml/min*

 -  Signs of acute heart failure within 24 hours of scheduled infusion

 -  History of aortic valve regurgitation classified as "moderate-severe" or worse

 -  Patients will be excluded who have:

 -  Known prior trauma to the coronary sinus

 -  In dwelling instrumentation that may hamper coronary venous catheterization,
 including a biventricular pacing coronary sinus lead

 -  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 with persistent (per ACC/AHA/EEC guidelines)53, defined as recurrent AF
 episodes lasting longer than 7 days) 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

 -  Inability to undergo 6 minute walk or treadmill exercise test

 -  Previous solid organ transplant

 -  Subjects with greater than 40% univentricular RV Pacing

 -  Subjects with uncontrolled diabetes defined as HbA1c >10 %

 -  Participation in an experimental clinical trial within 30 days prior to enrollment

 -  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 will be excluded
 unless:

 -  The subject is a carrier for hepatitis B/C but has never had an active flare

 -  Subjects with a history of Systemic Lupus Erythematosus (SLE) flare

 -  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 at day 0

 -  Critical limb ischemia that limits the patients from completing 6 minute walk or
 treadmill testing

 -  Subjects with severe chronic obstructive pulmonary disease (COPD)

 -  Severe defined as having been hospitalized for COPD within the last 12 months

 -  Any subject requiring home oxygen use for treatment of the symptoms of COPD

 -  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