Study Assessing Left Ventricular Administration of a Genetic Medicine Directing Organ Regeneration in Heart Failure

Prior treatment

• Prior heart transplant, history of LV reduction surgery, cardiomyoplasty, passive restraint device
• Had an acute myocardial infarction within the prior 30 days before initiation of screening;
• Unstable angina pectoris within 30 days before initiation of screening procedures;
• Received cell-based therapy from any source;
• Received any viral vector mediated gene therapy;
• Presence of a pacemaker or ICD generator with any of the following limitations/conditions:
  • manufactured before the year 2000
  • leads implanted \< 6 weeks prior to screening
  • non-transvenous epicardial leads
  • subcutaneous ICDs
  • any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated;
• A cardiac resynchronization therapy (CRT) device implanted \< 3 months prior to consent;
• Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell and gene-based therapies) or device trial;

Other illness

• Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent;
• Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial constriction; amyloidosis; or uncorrected thyroid disease;
• A history of ischemic or hemorrhagic stroke within 90 days of screening;
• An underlying autoimmune disorder or current immunosuppressive therapy;
• A contrast allergy that cannot adequately be managed by premedication;
• Evidence of active systemic infection at time of study product delivery;
• HIV and/or active HBV, HCV or Covid-19 infection at screening or baseline;
• A history of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months;
• Active malignancy within the past 3 years (exceptions: localized prostate cancer, cervical or breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated);

Lab values

• Liver dysfunction, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal;
• A baseline eGFR \<35 mL/min/1.73m2;
• Diabetes with poorly controlled blood glucose levels (HbA1c \> 10%);
• Coagulopathy (INR \> 1.5) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors); Subjects who cannot be withdrawn from anticoagulation will be excluded;

Other

• To participate, a subject MUST NOT HAVE:
• Aortic stenosis with valve area ≤ 1.5cm2;
• Idiopathic, valvular, peri/post-partum cardiomyopathy or other cardiomyopathy of non-ischemic etiology;
• A hematologic abnormality during baseline testing;
• Presence of LV thrombus;
• Other MRI contraindications
• Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent;
• Cognitive or language barriers that prohibit obtaining informed consent or any study elements;
• Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation;
• Expected survival \< 1 year in the judgment of the investigator;

• To participate, a subject MUST:
• Be ≥ 18 and \< 80 years of age;
• Have medically stable heart failure of ischemic etiology, secondary to MI with NYHA class II or III symptoms for at least 12 months before the initiation of screening procedures;
• Have a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 40% by cMRI at screening and baseline;
• The subject is not a candidate for either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery as determined by the principal investigator (or designee) in consultation with an interventional cardiologist during the screening period;
• Be on stable, outpatient, maximally tolerated guideline directed medical therapy (GDMT) for HF for 6 weeks, unless contraindicated, and remain stable during the screening period;
• Left ventricular (LV) end diastolic wall thickness of at least 8mm at the potential myocardial site for injection;
• Be a candidate for cardiac catheterization;
• Agree to protocol defined requirements for contraception;
• Provide written informed consent.