NAN-101 in Patients With Class III Heart Failure

Inclusion criteria:

1. Age >18 years of age
2. Chronic non-ischemic cardiomyopathy
3. LVEF ≤ 30% by transthoracic echocardiography (TTE) within 6 months prior to enrollment

NYHA Class III HF for a minimum of 6 months HF despite appropriate medical therapy (defined below):

1. Treatment with appropriate HF therapy as tolerated, including, but not limited to:
2. Beta blocker therapy and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment. May also receive aldosterone antagonist therapy. Doses of the above medications must be stable for ≥ 30 days prior to enrollment; and
3. Cardiac resynchronization therapy (CRT), if clinically indicated, must have been implanted ≥ 90 days prior to enrollment. Internal cardioverter defibrillator (ICD) must be implanted, if clinically indicated ≥ 30 days prior to enrollment
4. Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after IP administration:
5. Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to IP administration
6. Intrauterine device in place for at least 90 days prior to receiving IP
7. Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving IP
8. Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving IP). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
9. Surgical sterilization of the partner(s) (vasectomy) for >180 days prior to IP administration
10. Hormonal contraceptives starting > 90 days prior to IP. If hormonal contraceptives are started less than 90 days prior to receiving IP, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives
11. Males subjects capable of fathering a child:
12. Must agree to use a condom from IP administration through 6 months after the time of IP administration
13. Must agree not to donate sperm for 6 months after time of receiving IP
14. Documented evidence of vasectomy in males for 180 days minimum prior to receiving IP is an acceptable form of contraception
15. Males who claim abstinence as their method of contraception are allowed provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
16. Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form
17. Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist

Exclusion Criteria:

1. Chronic ischemic cardiomyopathy
2. Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
3. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
4. Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to enrollment
5. Third degree heart block
6. Clinically significant myocardial infarction (MI) in the judgment of the subject's physician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
7. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
8. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing
9. Known hypersensitivity to contrast dyes used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography
10. Expected survival < 1 year in the judgment of the investigator
11. Active or suspected infection within 48 hours prior to enrollment as evidenced by fever or positive culture
12. Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is negative, subject may be eligible (confirm with medical monitor).
13. Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) > 2x upper limit of normal (ULN) within 30 days prior to enrollment.
14. Renal Failure, dialysis dependent or serum creatinine > 2.5 mg/dl within 30 days prior to enrollment
15. Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μL within 30 days prior to enrollment
16. Anemia defined as hemoglobin <10 g/dL or transfusion dependent within 30 days prior to enrollment
17. Neutropenia defined as absolute neutrophils <1500 mm3 within 30 days prior to enrollment
18. Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
19. Previous participation in a study of gene transfer
20. Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of another investigational drug administration prior to administration of NAN-101 that may impact the therapeutic potential of NAN-101.
21. Pregnancy or breastfeeding at the time of screening