Lomecel-B Delivered During Stage II Surgery for Hypoplastic Left Heart Syndrome (ELPIS) (ELPIS)

This study is designed to assess the safety, tolerability, and efficacy of Lomecel-B as an adjunct therapy to the standard stage II (BDCPA) surgical intervention for HLHS. Lomecel-B will be delivered via intramyocardial injections

This study is designed to assess the safety, tolerability, and efficacy of Lomecel-B (formerly LMSCs) as an adjunct therapy to the standard stage II (BDCPA) surgical intervention for HLHS, which is typically performed at 4 - 6 months after birth. Lomecel-B will be delivered via intramyocardial injections. A total of 30 patients will be enrolled in 2 stages with 3 Cohorts. In the first stage, 10 consecutive HLHS patients will be enrolled and treated with Lomecel-B (Cohort A). The first 3 patients will be treated no less than 5 days apart, and will be evaluated for any treatment-emergent adverse events (TE-AEs) (e.g., induced myocardial infarction or perforation). These patients will undergo full evaluation for 5 days to demonstrate safety prior to proceeding with the remainder of the cohort. After 6 months post-treatment of the last patient of Cohort A, a formal safety review will be conducted prior to proceeding to the next phase. The second stage is double-blinded, in which 20 HLHS patients will be randomized to either receive treatment with Lomecel-B (Cohort B, 10 patients), or will receive no cells and no injection (Cohort C, 10 patients).

Phase 1: 10 patient safety run-in: all patients treated with LMSCs during Stage II surgery. Phase 2: 20 patients randomized 1:1 to receive either LMSCs or no cells (controls) during Stage II surgery.

Phase 1: no masking. Phase 2: HLHS patients which will be randomized to the treatment and control arms in a 1:1 ratio

10 consecutive HLHS patients will be enrolled and treated with Longeveron Mesenchymal Stem Cells (LMSCs). A single administration of LMSCs will be performed via intramyocardial injections during the Stage II (BDCPA) surgery. Dosing is based on body weight. Each LMSC-treated patient will be given 2.5 x 105 LMSCs per kg of body weight. The entire dose of the cells will be roughly 600 microliters.

Double-blinded, in which 20 HLHS patients will be randomized to either receive treatment with Longeveron Mesenchymal Stem Cells (LMSCs) (Cohort B, 10 patients) performed via intramyocardial injections during the Stage II (BDCPA) surgery, or will receive no cells and no injection (Cohort C, 10 patients) during the Stage II (BDCPA) surgery. The second stage is to obtain preliminary safety and efficacy data the will enable and guide a subsequent larger Phase 2 trial.

Double-blinded, in which 20 HLHS patients will be randomized to either receive treatment with Longeveron Mesenchymal Stem Cells (LMSCs) (Cohort B, 10 patients) performed via intramyocardial injections during the Stage II (BDCPA) surgery, or will receive no cells and no injection (Cohort C, 10 patients) during the Stage II (BDCPA) surgery. The second stage is to obtain preliminary safety and efficacy data the will enable and guide a subsequent larger Phase 2 trial.

Safety: To evaluate the safety and feasibility of intramyocardial injection of LMSCs during the Stage II (BDCPA) operation for HLHS via incidence of Treatment-Emergent Serious Adverse Events.

The incidence of Treatment-Emergent Serious Adverse Events will be evaluated, including: sustained/symptomatic ventricular tachycardia requiring intervention with inotropic support; aggravation of heart failure; myocardial infarction; unplanned cardiovascular operation for cardiac tamponade; infection during the first month post-treatment; and death.

Efficacy: Number of patients with Treatment-Emergent Adverse Events, and total number of occurrences of Treatment-Emergent Adverse Events, through-out participation in trial.

Treatment-Emergent Adverse Events will be assessed via incidence of co-morbidity, which include: cardiovascular morbidity; need for transplantation; re-hospitalizations; cardiovascular mortality; and all-cause mortality.

Inclusion Criteria: all patients must have HLHS (all types) requiring BDCPA surgery. Exclusion Criteria: all patients must not have any of the following. Significant coronary artery sinusoids. Requirement for mechanical circulatory support prior to BDCPA surgery. Underlying evidence of arrhythmia requiring anti-arrhythmia therapy. Need for concomitant surgery for aortic coarctation or tricuspid valve repair. HLHS and restrictive or intact atrial septum. Undergoing the Stage I (Norwood) procedure that does not have HLHS. Serum positivity for: HIV; hepatitis B virus surface antigen (HBV BsAg); and/or viremic hepatitis C virus (HCV). Parent/guardian that is unwilling or unable to comply with necessary follow-up. Unsuitability for the study based on the Investigator's clinical opinion. Documented chromosomal abnormalities