study to evaluate the safety and efficacy of jvs-100 administered to adults with ischemic heart failure

Conditions: Ischemic Heart Failure

Summary: 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.

Eligibility criteria:
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