Autologous Induced Pluripotent Stem Cells of Cardiac Lineage for Congenital Heart Disease

Individuals may be considered eligible for enrollment for Part I of this study (Skin Punch Biopsy) if in the best judgment of the Principal Investigator they will meet eligibility criteria outlined below at the time it is determined acceptable investigational product is available for administration (approximately 9 months post skin punch biopsy). Inclusion and exclusion criteria apply to both the treatment and control arms of the study unless otherwise specified.

Inclusion criteria

Individuals who meet all the following criteria are eligible for enrollment as study participants:

• Age 18 to 40 years old
• Subject must be able to understand and provide informed consent.
• Univentricular congenital heart disease.
• End-stage systolic heart failure, defined as Class IV according to New York Heart Association (NYHA) with abnormal visually estimated ejection fraction below 40%.
• Prognosis of 1 to 1.5 years survival at time of skin biopsy.
• The patient falls into one of the following categories:

• Currently listed for heart transplantation at an accredited program in the US but has an expected waiting time for a suitable organ that is likely longer than anticipated life-expectancy.
• Has been denied access to a heart transplantation at an accredited US institution.
• Is currently on or planning to be on mechanical support as destination therapy.
• All guideline directed therapy available to the subject has been maximized, for a minimum of 3 months prior to enrollment.
• Adequate social support system that facilitates subject participation in all study required tests and procedures and supports the subject's ability to comply with long-term study requirements.

Exclusion criteria

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

• No available autologous iPSC-CL as defined by the manufacturer's release criteria. (This applies to Part II of the study and applies to the treatment arm only.)
• History of symptomatic episodes of cardiac arrythmia requiring cardiac defibrillation or escalation of medications.
• Heart failure with preserved ejection fraction.
• Heart failure due to co-morbid conditions (e.g., amyloidosis, valvular heart disease, refractory anemia).
• QTc greater than 500 ms.
• Stage III or higher chronic kidney disease.
• History of liver cirrhosis.
• History of coronary artery disease.
• Uncontrolled diabetes mellitus.
• Any history of cancer.
• Contraindication for use of amiodarone for up to 3 months (treatment arm only).
• Contraindication for insertion of Insertable Cardiac Monitor.
• Contraindication for placement of LifeVest cardioverter defibrillator.
• Positive serology testing for HIV, Hepatitis B, Hepatitis C or Syphilis.
• Obesity with BMI greater than 30.
• Current alcohol or drug abuse precluding heart transplantation.
• Active infection requiring ongoing treatment.
• Contraindication to anesthesia.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality of the data obtained from the study.
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• History of non-compliance.
• Inability to be accompanied around the clock for any part of the first 3 weeks post product administration.
• Uncontrolled depression.
• Denied heart transplant due to social determinants.
• Current participation in another cardiac interventional clinical trial that could confound the results of this study.
• Previous heart transplant.