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

Phase 2Active Not RecruitingNCT04925024

Longeveron Inc.40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Hypoplastic Left Heart Syndrome

Interventions

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.

Eligibility

Sex: ALLMax age: 12 Months

Medical Language ↔ Plain English

Inclusion: All participants must have HLHS (includes all types) requiring Stage II palliation (Glenn or Hemi-Fontan operation). Exclusion: 1. Requirement for ongoing mechanical circulatory support immediately prior to Stage II palliation within 5 days 2. Need for concomitant surgery for aortic coarctation or tricuspid valve repair or Endocardial fibroelastosis (EFE) resection or left ventricle recruitment procedures 3. Undergoing the Stage I (Norwood) procedure that does not have HLHS 4. 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: 1. Documented history of mother's testing conducted during pregnancy 2. Documented history of participants testing. 3. If above documentation is not available blood will be obtained from participant at Screening/Baseline. 5. Parent/guardian that is unwilling or unable to comply with necessary follow-up 6. Unsuitability for the study based on the Investigator's clinical opinion 7. Known hypersensitivity to dimethyl sulfoxide (DMSO) 8. Presence of a pacemaker, or anticipated placement of a pacemaker, at the time of the Stage II palliation

Locations (10)

Children's Hospital of Los Angeles

Los Angeles, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Advocate Children's Hospital

Chicago, Illinois, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Nebraska

Omaha, Nebraska, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Primary Children's Hospital/University of Utah

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline, 12 Months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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: all-cause mortality; 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; sepsis; need for new permanent pacemaker; stroke or embolic event to the brain

Time frame: 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 worsening heart failure; listed for heart transplant; heart failure hospitalization; cardiovascular mortality

Time frame: Baseline, 12 Months