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

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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Lomecel-B Injection in Patients With Hypoplastic Left Heart Syndrome: A Phase I/II Study (ELPIS)

Conditions
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HLHS

Intervention / Treatment
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* Biological: Longeveron Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A - Phase 1 (Open Label)<br>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. | Biological: Longeveron Mesenchymal Stem Cells<br>* Allogeneic bone marrow-derived mesenchymal stem cell<br>* Other names: LMSCs;|
| Experimental: Cohort B - Phase 2 Treatment Group<br>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. | Biological: Longeveron Mesenchymal Stem Cells<br>* Allogeneic bone marrow-derived mesenchymal stem cell<br>* Other names: LMSCs;|
| No Intervention: Cohort C - Phase 2 Control Group<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Evaluated through 1 year post-treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Change from baseline in right ventricular ejection fraction (%). | Used to assess cardiac function. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change from baseline in right ventricular end-systolic volume. | Used to assess cardiac function. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change from baseline in right ventricular end-diastolic volume. | Used to assess cardiac function. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change from baseline in right ventricular end-diastolic diameter. | Used to assess cardiac function. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change from baseline tricuspid regurgitation. | Used to assess cardiac function. Measured by serial echocardiograms and MRI. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change in weight (in kilograms). | Used to assess change in somatic growth. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change in height (in centimeters). | Used to assess change in somatic growth. | Evaluated through 1 year post-treatment. | 
| Efficacy: Change in head circumference (in centimeters). | Used to assess change in somatic growth. | Evaluated through 1 year post-treatment. | 
| 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. | Evaluated through 1 year post-treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatrics