Evaluation of Lomecel-B™ Injection in Patients With Hypoplastic Left Heart Syndrome: A Phase IIb Clinical Trial.

Study Overview
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Brief Summary
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The purpose of this study is to test whether Lomecel-B™ works in treating patients with hypoplastic left heart syndrome (HLHS) and to gather additional information about the safety of Lomecel-B. Lomecel-B contains human mesenchymal stem cells (MSCs) as the active ingredient. MSCs are special cells in the body that are able to change into other types of cells, such as heart, blood, and muscle cells. MSCs are found in various tissues of the body, such as the bone marrow, which is the spongy tissue inside of your bones. Lomecel-B uses MSCs from bone marrow of unrelated young healthy donors. These are called allogeneic, and do not require donor matching to the patient.

Official Title
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Evaluation of Lomecel-B™ Injection in Patients With Hypoplastic Left Heart Syndrome: A Phase IIb Clinical Trial.

Conditions
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Hypoplastic Left Heart Syndrome

Intervention / Treatment
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* Biological: Lomecel-B medicinal signaling cells


Participation Criteria
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Eligibility Criteria
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Inclusion: All participants must have HLHS (includes all types) requiring Stage II palliation (Glenn or Hemi-Fontan operation). Exclusion: Requirement for ongoing mechanical circulatory support immediately prior to Stage II palliation within 5 days Need for concomitant surgery for aortic coarctation or tricuspid valve repair or Endocardial fibroelastosis (EFE) resection or left ventricle recruitment procedures Undergoing the Stage I (Norwood) procedure that does not have HLHS Serum positivity for: human immunodeficiency virus (HIV); hepatitis B virus surface antigen (HBV BsAg); and/or viremic hepatitis C virus (HCV). This criterion can be ascertained by one of three ways: Documented history of mother's testing conducted during pregnancy Documented history of participants testing. If above documentation is not available blood will be obtained from participant at Screening/Baseline. Parent/guardian that is unwilling or unable to comply with necessary follow-up Unsuitability for the study based on the Investigator's clinical opinion Known hypersensitivity to dimethyl sulfoxide (DMSO) Presence of a pacemaker, or anticipated placement of a pacemaker, at the time of the Stage II palliation

Ages Eligible for Study
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Maximum Age: 12 Months

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lomecel B Group<br>Participants randomized to receive Lomecel-B injections during their Stage II palliation. | Biological: Lomecel-B medicinal signaling cells<br>* A single administration of Lomecel-B will be performed via 6-10 intramyocardial injections into the right ventricle during the participant's standard of care stage II palliation. Dosing is based on body weight. Each patient will be given 2.5 x 10^5 cells per kg of body weight. The entire dose of the cells will be roughly 600 microliters.<br>|
| No Intervention: No Study Intervention Control Group<br>Participants randomized to receive no study intervention during their Stage II palliation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in right ventricular ejection fraction (RVEF) | Efficacy will be reported as change in right ventricular ejection fraction (RVEF) assessed as a percentage and will be measured via cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in right ventricular ejection fraction (RVEF) | Efficacy will be reported as change in right ventricular ejection fraction (RVEF) assessed as a percentage and will be measured via cardiac magnetic resonance (CMR) imaging. | Baseline, 6 Months | 
| Change in right ventricular mass index at diastole | Efficacy will be reported as change in right ventricular mass index at diastole assessed as g/m^2 and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right ventricular end-diastolic volume index (RVEDVI) | Efficacy will be reported as change in right ventricular end diastolic volume index (RVEDVI) assessed as ml/m^2 and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right ventricular end-systolic volume index (RVESVI) | Efficacy will be reported as change in right ventricular end systolic volume index (RVESVI) assessed as ml/m^2 and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right ventricular global longitudinal strain and strain rate | Efficacy will be reported as change in right ventricular global longitudinal strain and strain rate assessed as % and s^-1 respectively and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right ventricular global circumferential strain and strain rate | Efficacy will be reported as the change in right ventricular global circumferential strain and strain rate as % and s^-1 respectively, and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right atrial volume index | Efficacy will be reported as the change in right atrial volume index as ml/m^2 and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in right ventricular work index | Efficacy will be reported as the change in right ventricular work index as (mmHg x mL x beats) / min and will be measured via serial cardiac magnetic resonance (CMR) imaging. | Baseline, 12 Months | 
| Change in tricuspid regurgitation severity | Efficacy will be reported as change in the categorical qualitative assessment of tricuspid valve regurgitation (trivial, mild, moderate, severe) and will be measured via transthoracic echocardiography. | Baseline, 12 Months | 
| Change in RV compliance/diastolic function | Efficacy will be reported as change in diastolic function as measured by the tricuspid E/E' ratio, evaluating the tricuspid inflow E and A velocities and ratio, and tricuspid annular DTI E'A' velocities. Function reported as normal diastolic function (no abnormalities in these measures), mildly impaired diastolic function (1 abnormal measure), moderately impaired diastolic function (2 abnormal measures), and severely impaired diastolic function (3 abnormal measures). These measures will be measured via transthoracic echocardiography. | Baseline, 12 Months | 
| Change in weight | Efficacy measured as change in participant's weight in kg and will be measured serially to assess change in somatic growth. | Baseline, 12 Months | 
| Change in length (height) | Efficacy measured as change in participant's length (height) in cm and will be measured serially to assess change in somatic growth. | Baseline, 12 Months | 
| Change in head circumference | Efficacy measured as change in participant's head circumference in cm and will be measured serially to assess change in somatic growth. | Baseline, 12 Months | 
| Change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) | Efficacy measured as change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in pg/ml and will be measured serially by blood draw. | Baseline, 12 Months | 
| Change in modified Ross Heart Failure Classification score | The Ross Heart Failure Classification provides a global assessment of heart failure severity in infants. Efficacy measured as change in classification and will be measured serially via physician's assessment using the modified Ross Heart Failure Classification; classifications defined as Class 1 (no limitations of physical activity); Class 2 (may experience symptoms during moderate exercise but not during rest); Class 3 (symptoms with minimal exertion that interfere with normal daily activity); Class 4 (unable to carry out physical activity/has symptoms at rest that worsen with exertion). | Baseline, 12 Months | 
| Change in PedsQL™ Infant Scales | The PedsQL™ Infant Scales is a generic health related quality of life instrument specifically for healthy and ill infants ages 1-24 months. Efficacy measured as change in PedsQL total improvement score and will be measured serially by parental proxy-report. Higher scores are indicative of better quality of life. | Baseline, 12 Months | 
| Freedom from unplanned catheter intervention needed to address the pulmonary arteries or aorta. | Efficacy measured as the number and percentage of participants who do not undergo unplanned catheter interventions to address pulmonary arteries or the aorta. | Baseline, 12 Months | 
| Change in biomarkers/cytokines | Efficacy measured as change in biomarkers/cytokines in pg/ml and/or ng/ml and will be measured serially by blood draw. | Baseline, 12 Months | 
| Participants experiencing treatment emergent serious adverse events (TE-SAEs) | Safety will be reported as the number of participants experiencing treatment emergent serious adverse events (TE-SAEs) assessed by treating physician within the 30 days following study procedure. These include: greater than 30 seconds of sustained/symptomatic ventricular tachycardia requiring intervention; cardiogenic shock; unplanned cardiovascular operation for bleeding due to right ventricular intramyocardial injection site bleeding in the first five days after stage II palliation; worsening of cardiac function; local infection or systemic infection; need for new permanent pacemaker; death. | 30 days post Stage II palliation | 
| Participants experiencing major adverse cardiac events (MACE) | Safety will be reported as the number of participants with adjudicated events including cardiovascular morbidity; need for transplantation; re-hospitalizations; cardiovascular mortality; all-cause mortality. | Baseline, 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoplastic Left Heart Syndrome, Pediatrics, Heart Defects, Congenital Cardiovascular Diseases, Stem Cells