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

• ClinicalTrials.gov Identifier: NCT04925024
• Recruitment Status: Recruiting
• First Posted: June 14, 2021
• Last Update Posted: April 9, 2024
• Sponsor: Longeveron Inc.
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Ann & Robert H Lurie Children's Hospital of Chicago; The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Longeveron Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypoplastic Left Heart Syndrome	Biological: Lomecel-B medicinal signaling cells	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Evaluation of Lomecel-B™ Injection in Patients With Hypoplastic Left Heart Syndrome (HLHS) : A Phase IIb Clinical Trial.
• Actual Study Start Date: June 25, 2021
• Estimated Primary Completion Date: March 2025
• Estimated Study Completion Date: August 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lomecel B Group; Participants randomized to receive Lomecel-B injections during their Stage II palliation.	Biological: Lomecel-B medicinal signaling cells; 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.
No Intervention: No Study Intervention Control Group; Participants randomized to receive no study intervention during their Stage II palliation.

Outcome Measures

Primary Outcome Measures :

1. Change in right ventricular ejection fraction (RVEF) [ Time Frame: Baseline, 12 Months ]
   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.

Secondary Outcome Measures :

1. Change in right ventricular ejection fraction (RVEF) [ Time Frame: Baseline, 6 Months ]
   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.
2. Change in right ventricular mass index at diastole [ Time Frame: Baseline, 12 Months ]
   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.
3. Change in right ventricular end-diastolic volume index (RVEDVI) [ Time Frame: Baseline, 12 Months ]
   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.
4. Change in right ventricular end-systolic volume index (RVESVI) [ Time Frame: Baseline, 12 Months ]
   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.
5. Change in right ventricular global longitudinal strain and strain rate [ Time Frame: Baseline, 12 Months ]
   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.
6. Change in right ventricular global circumferential strain and strain rate [ Time Frame: Baseline, 12 Months ]
   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.
7. Change in right atrial volume index [ Time Frame: Baseline, 12 Months ]
   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.
8. Change in right ventricular work index [ Time Frame: Baseline, 12 Months ]
   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.
9. Change in tricuspid regurgitation severity [ Time Frame: Baseline, 12 Months ]
   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.
10. Change in RV compliance/diastolic function [ Time Frame: Baseline, 12 Months ]
    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.
11. Change in weight [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as change in participant's weight in kg and will be measured serially to assess change in somatic growth.
12. Change in length (height) [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as change in participant's length (height) in cm and will be measured serially to assess change in somatic growth.
13. Change in head circumference [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as change in participant's head circumference in cm and will be measured serially to assess change in somatic growth.
14. Change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as change in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in pg/ml and will be measured serially by blood draw.
15. Change in modified Ross Heart Failure Classification score [ Time Frame: Baseline, 12 Months ]
    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).
16. Change in PedsQL™ Infant Scales [ Time Frame: Baseline, 12 Months ]
    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.
17. Freedom from unplanned catheter intervention needed to address the pulmonary arteries or aorta. [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as the number and percentage of participants who do not undergo unplanned catheter interventions to address pulmonary arteries or the aorta.
18. Change in biomarkers/cytokines [ Time Frame: Baseline, 12 Months ]
    Efficacy measured as change in biomarkers/cytokines in pg/ml and/or ng/ml and will be measured serially by blood draw.
19. Participants experiencing treatment emergent serious adverse events (TE-SAEs) [ Time Frame: 30 days post Stage II palliation ]
    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.
20. Participants experiencing major adverse cardiac events (MACE) [ Time Frame: Baseline, 12 Months ]
    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.

Eligibility Criteria

• Ages Eligible for Study: up to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Stephanie Brazis, MPH; 312-227-0201; sbrazis@luriechildrens.org

Contact: Kiran Mansoor, MBBS; 713-500-9643; Kiran.Mansoor@uth.tmc.edu

Locations

United States, California

Children's Hospital of Los Angeles; Recruiting

Los Angeles, California, United States, 90027

Contact: Carly Weaver 323-361-8631 cweaver@chla.usc.edu

Contact: Brandi Scott 323-361-7086 bscott@chla.usc.edu

Principal Investigator: John Cleveland, MD

United States, Georgia

Children's Healthcare of Atlanta; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Emily Klingman, MSN, RN 404-785-7153 emily.klingman@choa.org

Contact: Rachna Prasad 404-785-7294 Rachna.Prasad@choa.org

Principal Investigator: William Mahle, MD

United States, Illinois

Advocate Children's Hospital; Terminated

Chicago, Illinois, United States, 60453

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

Chicago, Illinois, United States, 60611

Contact: Carmen Diaz-Leos 312-227-5395 cdiazleos@luriechildrens.org

Contact: Stephanie Brazis 312-227-0201 sbrazis@luriechildrens.org

Principal Investigator: Kiona Allen, MD

United States, Massachusetts

Boston Children's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Michael Bamgbose 617-919-4457 Michael.Bamgbose@cardio.chboston.org

Contact: Jonah Leighton 617-919-4457 Jonah.Leighton@childrens.harvard.edu

Principal Investigator: Sitaram Emani, MD

United States, Nebraska

Children's Nebraska; Recruiting

Omaha, Nebraska, United States, 68114

Contact: Morgan Loeffelbein 402-889-2822 mloeffelbein@unmc.edu

Principal Investigator: Ram K Subramanyan, MD, PhD

United States, Ohio

Cincinnati Children's Hospital Medical Center; Terminated

Cincinnati, Ohio, United States, 45229

United States, Texas

UTHealth-McGovern Medical School; Recruiting

Houston, Texas, United States, 77030

Contact: Rebecca Sam 713-500-5746 Rebecca.M.Sam@uth.tmc.edu

Contact: Rosie Munoz 713-500-7510 Rosie.Munoz@uth.tmc.edu

Principal Investigator: Damien LaPar, MD

United States, Utah

Primary Children's Hospital/University of Utah; Recruiting

Salt Lake City, Utah, United States, 84113

Contact: Linda Lambert, ARPN 801-587-7523 Linda.lambert@hsc.utah.edu

Principal Investigator: Adil Husain, MD

Principal Investigator: Edem Binka, MD

Sponsors and Collaborators

Longeveron Inc.

National Heart, Lung, and Blood Institute (NHLBI)

Ann & Robert H Lurie Children's Hospital of Chicago

The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Stu Berger, MD; Ann & Robert H Lurie Children's Hospital of Chicago

More Information

Additional Information:

ELPIS II study website 

Earlier phase I study (ELPIS) 

Publications:

Kaushal S, Hare JM, Hoffman JR, Boyd RM, Ramdas KN, Pietris N, Kutty S, Tweddell JS, Husain SA, Menon SC, Lambert LM, Danford DA, Kligerman SJ, Hibino N, Korutla L, Vallabhajosyula P, Campbell MJ, Khan A, Naioti E, Yousefi K, Mehranfard D, McClain-Moss L, Oliva AA, Davis ME. Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial. Eur Heart J Open. 2023 Jan 11;3(2):oead002. doi: 10.1093/ehjopen/oead002. eCollection 2023 Mar.

• Responsible Party: Longeveron Inc.
• ClinicalTrials.gov Identifier: NCT04925024
• Other Study ID Numbers: 2021-4531; 7UG3HL148318-02 ( U.S. NIH Grant/Contract ); 1U24HL148316-01A1 ( U.S. NIH Grant/Contract )
• First Posted: June 14, 2021
• Last Update Posted: April 9, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Longeveron Inc.:

Hypoplastic Left Heart Syndrome; Pediatrics; Heart Defects; Congenital Cardiovascular Diseases; Stem Cells

Additional relevant MeSH terms:

Hypoplastic Left Heart Syndrome; Syndrome; Disease; Pathologic Processes; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities