Ischemic Heart Failure
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICAL45 mg dose of JVS-100
Coronary Sinus Delivery
BIOLOGICALPlacebo
Coronary Sinus Delivery
BIOLOGICAL30 mg dose of JVS-100
Coronary Sinus Delivery
Sponsors
Juventas Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of JVS-100 delivery on 6 minute walk distance at 4 month follow-up | 4 Months | To investigate the impact of single doses of JVS-100 (either 30 or 45 mg) delivered retrograde via the coronary sinus through the Oscor Venos Occlusion Balloon catheter on 6 minute walk distance compared to placebo at 4 months post dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of JVS-100 delivery on heart failure symptoms compared to placebo at 4 and/or 12 month follow-up | 4 and/or 12 months | To assess the impact of a single dose of JVS-100 on heart failure symptoms compared to placebo at 4 and/or 12 months post-dosing. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Impact of JVS-100 delivery on quality of life measure at 4 month follow-up | 4 Months | To investigate the impact of single doses of JVS-100 (either 30 or 45 mg) delivered retrograde via the coronary sinus through the Oscor Venos Occlusion Balloon catheter on quality of life measure compared to placebo at 4 months post dosing. |
Countries
United States
Outcome results
None listed