Single or Repeated Intravenous Administration of umbiliCAl Cord Mesenchymal sTrOmal Cells in Ischemic Cardiomyopathy

Prior treatment

• Indication for standard of care surgery (including valve surgery, placement of left ventricular assist device, or imminent heart transplantation), coronary artery bypass grafting (CABG) procedure, and/or percutaneous coronary intervention (PCI) for the treatment of ischemic and/or valvular heart disease. Subjects who require or undergo PCI should undergo these procedures a minimum of 3 months in advance of randomization. Subjects who require or undergo CABG should undergo these procedures a minimum of 3 months in advance of randomization. In addition, subjects who develop a need for revascularization following enrollment should undergo revascularization without delay. Indication for imminent heart transplantation is defined as a high likelihood of transplant prior to collection of the 12 month study endpoint. Candidates cannot be UNOS 1A or 1B, and they must have documented a low probability of being transplanted.
• Presence of a pacemaker and/or implantable cardiac device (ICD) generator with any of the following limitations/conditions:
  • manufactured before the year 2000
  • leads implanted \< 6 weeks prior to consent
  • non transvenous epicardial or abandoned leads
  • subcutaneous ICDs (if not MRI compatible)
  • leadless pacemakers
  • any other condition that, in the judgment of device trained staff, would deem an MRI contraindicated
• A cardiac resynchronization therapy (CRT) device implanted less than 3 months prior to consent.
• Received gene or cell based therapy from any source within the previous 12 months.

Other illness

• Severe valvular (any valve) insufficiency and/or regurgitation within 12 months of consent
• History of ischemic or hemorrhagic stroke within 90 days of consent
• HIV and/or active HBV or HCV
• Known history of anaphylactic reaction to penicillin or streptomycin
• History of malignancy within 2 years (i.e., subjects with prior malignancy must be disease free for 2 years), excluding basal cell carcinoma and cervical carcinoma in situ which have been definitively treated.
• Condition that limits lifespan to \< 1 year
• History of drug abuse (illegal "street" drugs except marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 12 months.
• Any other condition that, in the judgment of the Investigator or Sponsor, would impair enrollment, study product administration, or follow up.

Lab values

• Baseline glomerular filtration rate (eGFR) \< 35 ml/min/1.73m2
• Blood glucose levels (HbA1c) \>10%
• Hematologic abnormality evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet count \< 100,000/ul
• Liver dysfunction evidenced by enzymes (AST and ALT) ˃ 3 times the ULN.

Other

• Pacemaker dependence with an ICD (Note: pacemaker dependent candidates without an ICD are not excluded)
• Other MRI contraindications (e.g. patient body habitus incompatible with MRI)
• An appropriate ICD firing or anti tachycardia pacing (ATP) for ventricular fibrillation or ventricular tachycardia within 30 days of consent
• Ventricular tachycardia ≥ 20 consecutive beats without an ICD within 3 months of consent, or symptomatic Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent
• Evidence of active myocarditis
• Participation in an investigational therapeutic or device trial within 30 days of consent
• Cognitive or language barriers that prohibit obtaining informed consent or any study elements
• Pregnancy or lactation or plans to become pregnant in the next 12 months.

• Be ≥ 21 and ≤ 85 years of age.
• Have documented CAD (\> 70% lesion in at least 1 epicardial vessel) with evidence of myocardial injury, LV dysfunction, and clinical evidence of HF.
• Have a "detectable" area of myocardial injury defined as ≥ 5% LV involvement (infarct volume) and any subendocardial involvement by MRI.
• Have an EF ≤ 40% by MRI.
• Be receiving guideline driven medical therapy for HF (beta blockers, diuretics, ACE inhibitors or ARBs, or ARNIs, aldosterone antagonists, hydralazine isosorbide, sodium-glucose transporter 2 inhibitors) ) at stable, maximally tolerated doses for ≥ 1 month prior to consent. "Stable" is defined as stable dose with no changes for 30 days after last dose adjustment. For beta blockade "stable" is defined as no greater than a 50% reduction in dose or no more than a 100% increase in dose.
• Have NYHA class I, II or III symptoms of HF (see Appendix A)
• If a female of childbearing potential, be willing to use one form of birth control for the duration of the study and undergo a serum pregnancy test at baseline and within 36 hours prior to infusion