Phase
Condition
Heart Failure
Congestive Heart Failure
Chest Pain
Treatment
N/AClinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Age 18 to 80 years, inclusive, with history of heart failure (HF).
Current HF symptoms with NYHA Functional Classification Class II to IV (inclusive) atScreening (Visit 1).
Currently receiving optimally tolerated standard of care HF medical therapy as definedby the American Heart Association (AHA)/American College of Cardiology (ACC) HeartFailure guidelines and Focused Update along with an angiotensin converting enzymeinhibitor (ACEi)/angiotensin II receptor blockers (ARB), diuretics andsacubitril/valsartan for 4 weeks or longer, without change in drug therapy or dosageregimen, prior to Visit 1 (and continued same HF therapy through Visit 2).
Left Ventricular Ejection Fraction (LVEF) ≥ 10 to ≤ 35% as determined by Screeningechocardiogram (ECHO).
NT pro BNP ≥ 400 pg/mL.
If subject has had coronary artery bypass surgery, then at least one conduit must bepatent and therefore be amendable for test article.
Women of child bearing capacity must have a negative pregnancy test before 2 days oftest article administration and must not be currently breastfeeding or nursing, andfemale and male patients must be willing to use birth control for 12 weeks after testarticle administration if the female partner is of child bearing capacity. Acceptablemethods of effective birth control include total sexual abstinence; a condom withspermicide (men) in combination with barrier methods (diaphragm, cervical cap orcervical sponge); hormonal birth control (oral or injectable contraceptives);intrauterine devices; or surgical sterilization (vasectomy and testing that showsthere is no sperm in the semen for men and bilateral tubal ligation +/- oophorectomyfor women).
Willing to provide informed consent consistent with International Conference onHarmonisation Good Clinical Practices.
Exclusion
Exclusion Criteria:
Use of intravenous (IV) vasodilatory or inotropic therapy within 24 hours prior toVisit 2.
Unstable angina within 3 months of Visit 1.
Coronary revascularization planned or predicted within 6 months prior to Visit 1.
Subjects who are candidates for revascularization are not considered appropriate forthis trial; therefore, if a subject has Ischemia of viable myocardium > 15% and is acandidate for revascularization, this subject would not be eligible to participate inthis trial.
Myocardial infarction within 6 months prior to Screening (Visit 1). Myocardialinfarction is defined by documented evidence of a rise and/or fall of cardiacbiomarker values (preferably cardiac troponin) with at least one value above the 99thpercentile upper reference limit, and either ischemic symptoms, electrocardiogramchanges, imaging evidence of loss of viable myocardium or new regional wall motionabnormality, or identification of an intracoronary thrombus by coronary angiography.
Thrombocytopenia (< 100,000 platelets/µL) or bleeding diathesis.
Stroke or transient ischemic attack within 6 months prior to Screening (Visit 1).
Use of sodium-glucose co-transporter 2 inhibitors used to treat type 2 diabetesmellitus.
Cardiac:
Biopsy documenting reversible cause of cardiomyopathy within 6 months of Visit 1 (Screening) if available as part of patient's prior cardiac history.
Acute cardiac decompensation.
If coronary angiogram within 6 months, with a presence of untreated severe threevessel coronary disease or unprotected left main coronary artery disease orcoronary anatomy unsuitable for study procedure (eg, arterial tortuosity, etc)prior to Randomization (Visit 2).
Use of IV diuretics within 12 hours of Randomization (Visit 2).
Hemodynamically significant untreated valvular heart disease based on the AHA/ACCValvular Heart Disease Guidelines.
Current evidence of restrictive, peripartum, viral, infectious, infiltrative, orinflammatory cardiomyopathy.
Significant pericardial effusion at Screening (Visit 1) or at the time of testarticle administration.
Current untreated ventricular arrhythmias.
Currently awaiting planned heart transplantation or ventricular assist device.
Congenital heart disease (other than small or hemodynamically non significantventricular septal defect or atrial septal defect).
Device therapy as noted below: i. Cardiac resynchronization therapy (CRT), or CRT-D/P, is not allowed within 6 monthsof implantation. ii. Implantable Cardioverter Defibrillator or pacemaker implantation is not allowed ifimplanted < 30 days prior to Screening (Visit 1). iii. CardioMems device is not allowed. l. Systolic blood pressure ≥ 160 mm Hg or < 90 mm Hg at Visit 1 or 2. m. Diastolic blood pressure ≥ 95 mm Hg at Visit 1 or 2.
6 Minute Walk Test (6MWT):
Inability to perform the 6MWT for reasons unrelated to heart failure (eg,physical limitations, peripheral vascular disease).
Distance walked in 6MWT (6MWD) < 100 m
Pulmonary:
Pulmonary disease requiring oxygen therapy;
Severe chronic obstructive pulmonary disease; restrictive lung disease.
Upper respiratory infection within 4 weeks of Screening (Visit 1).
History of organ transplant.
Viral syndrome with fever ≥101° Fahrenheit (patient may be reconsidered for enrollment 4 weeks following resolution of viral syndrome).
History of human immunodeficiency virus or acquired immunodeficiency syndrome, historyof hepatitis C virus, or immunosuppressed by medicines (corticosteroids, methotrexate,cyclophosphamide, cyclosporine).
Presence of eGFR ≤ 30 mL/min/1.73 m2 using the Cockcroft Gault equation.
Patients with life expectancy < 1 year.
Documented Child Pugh B or C hepatic disease.
Body Mass Index ≥ 40 kg/m2.
Participation in any other clinical trial or registry within 30 days prior toRandomization (Visit 2).
Hemoglobin ≤ 10 gm/dL.
Prior history of malignancy.
Prior history of gene transfer.