Lomecel-B Injection for Hypoplastic Left Heart Syndrome

(ELPIS II Trial)

Recruiting at 7 trial locations

Overseen By Kiran Mansoor, MBBS

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Longeveron Inc.

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 30 days

38 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Lomecel-B Injection for Hypoplastic Left Heart Syndrome?

Research suggests that mesenchymal stem cells, like those in Lomecel-B, may help improve heart function in conditions similar to hypoplastic left heart syndrome by supporting the heart's ability to pump blood. Studies in animals and early human trials have shown potential benefits in heart function, which is promising for future treatment options. ^{1 2 3 4 5}

Is Lomecel-B Injection safe for humans?

The ELPIS trial is testing the safety of Lomecel-B (mesenchymal stem cells) in children with hypoplastic left heart syndrome by monitoring for major heart-related issues. This study aims to ensure the treatment is safe before moving to further testing. ^{1 4 6 7 8}

How is the Lomecel-B treatment different from other treatments for hypoplastic left heart syndrome?

Lomecel-B is unique because it uses mesenchymal stem cells (special cells that can develop into different types of cells) to potentially improve heart function in children with hypoplastic left heart syndrome, aiming to enhance the right ventricle's performance and possibly delay or avoid heart transplantation, unlike traditional surgical methods. ^{1 4 5 9 10}

Research Team

Stu Berger, MD

Principal Investigator

Ann & Robert H Lurie Children's Hospital of Chicago

Eligibility Criteria

This trial is for patients with Hypoplastic Left Heart Syndrome (HLHS) who are scheduled for Stage II heart surgery. It's not suitable for those unwilling to follow the study plan, with pacemakers, needing additional heart surgeries at the time of Stage II operation, or infected with HIV/HBV/HCV. People allergic to DMSO can't join.

Inclusion Criteria

I have HLHS and need a Stage II heart surgery.

Exclusion Criteria

I am having the Norwood procedure but do not have hypoplastic left heart syndrome.

I have a pacemaker or will get one before my Stage II treatment.

I need a device to help my heart pump blood right before my second heart surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lomecel-B injections during their Stage II palliation

30 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits (in-person and virtual)

Treatment Details

Interventions

• Lomecel-B

Trial Overview The trial tests Lomecel-B™, which contains human mesenchymal stem cells from bone marrow donors. These cells may transform into heart and other types of cells and could help treat HLHS by repairing heart tissue.

Participant Groups

Group I: Lomecel B Group Experimental Treatment 1 Intervention

Participants randomized to receive Lomecel-B injections during their Stage II palliation.

Group II: No Study Intervention Control Group Active Control 1 Intervention

Participants randomized to receive no study intervention during their Stage II palliation.

Lomecel-B is already approved in United States for the following indications:

Approved in United States as Lomecel-B for:

• None approved; under investigation for Hypoplastic Left Heart Syndrome (HLHS), Alzheimer’s Disease, and Aging-related Frailty

Who Is Running the Clinical Trial?

Longeveron Inc.

Lead Sponsor

Trials

10

Recruited

480+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Findings from Research

The ELPIS trial is investigating the safety and feasibility of injecting bone marrow-derived mesenchymal stem cells (MSCs) in 10 children with hypoplastic left heart syndrome (HLHS) to improve right ventricular function, with a focus on monitoring for major adverse cardiac events.

If the initial phase is successful, a larger phase IIb trial will compare MSC injection to standard surgical care in 20 patients, aiming to assess improvements in cardiac function and reduce the need for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome. Kaushal, S., Wehman, B., Pietris, N., et al.[2018]

Regenerative medicine approaches for treating hypoplastic left heart syndrome (HLHS) offer a promising alternative to current palliative care methods, potentially leading to curative treatments.

Despite the potential, significant challenges remain in translating these innovative strategies into clinical practice, necessitating further scientific and technological advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential Role of Regenerative Medicine on the Future Management of Hypoplastic Left Heart Syndrome. Kelly, JM., Anderson, C., Breuer, CK.[2023]

In a phase I trial involving 14 patients with ischemic heart disease, the direct injection of autologous bone marrow stromal cells (BMSCs) into the heart was found to be safe and technically feasible when combined with surgical revascularization procedures like TMR or CABG.

At 1 year post-treatment, patients showed improved cardiac function in the areas treated with BMSCs and reported enhanced quality of life, including significant reductions in angina symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intramyocardial Bone Marrow Stem Cells in Patients Undergoing Cardiac Surgical Revascularization. Chan, JL., Miller, JG., Zhou, Y., et al.[2021]

Stem cell therapy shows promise as a novel treatment for managing right ventricular dysfunction in patients with hypoplastic left heart syndrome, a serious congenital heart condition that often leads to significant morbidity after surgical palliation.

Current research indicates that the therapeutic effects of stem cells may primarily result from their paracrine effects—where they release signaling molecules—rather than from direct integration into heart tissue, which is a shift in understanding that could influence future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions. Bittle, GJ., Morales, D., Deatrick, KB., et al.[2020]

Injecting bone marrow mesenchymal stem cells (BMSCs) directly into the ventricular wall of rabbits with dilated cardiomyopathy significantly improved left ventricular function compared to control groups.

The study demonstrated that BMSCs could differentiate into cardiomyocytes, as indicated by cellular staining, confirming their presence and potential effectiveness in enhancing heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous bone marrow mesenchymal cell transplantation improves left ventricular function in a rabbit model of dilated cardiomyopathy. Chen, Y., Liu, W., Li, W., et al.[2018]

The CHILD trial is a Phase I/II study investigating the safety and efficacy of neonatal cardiac-derived progenitor cells (nCPCs) in infants with hypoplastic left heart syndrome (HLHS), aiming to enroll 32 patients across 4 institutions.

Preliminary findings suggest that nCPCs may improve right ventricle function, which is crucial since RV dysfunction is linked to higher mortality in HLHS infants, but the trial is still ongoing to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). Kaushal, S., Hare, JM., Shah, AM., et al.[2022]

An induced pluripotent stem cell (iPSC) line was successfully created from a female patient with hypoplastic left heart syndrome (HLHS) who has a specific NOTCH1 gene mutation, which is linked to this heart defect.

This iPSC line shows normal characteristics and differentiation potential, making it a valuable tool for studying the mechanisms behind NOTCH1-related HLHS and potentially developing targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of NCHi009-A, an iPSC line from a patient with hypoplastic left heart syndrome (HLHS) carrying a heterozygous NOTCH1 mutation. Adhicary, S., Ye, S., Lin, H., et al.[2023]

Intracoronary delivery of autologous cardiosphere-derived cells (CDCs) in 14 children with hypoplastic left heart syndrome was found to be feasible and safe, with no serious adverse events reported during an 18-month follow-up.

Patients receiving CDCs showed significant improvements in right ventricular ejection fraction and overall cardiac function compared to controls, suggesting potential benefits for long-term clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Ishigami, S., Ohtsuki, S., Tarui, S., et al.[2015]

An induced pluripotent stem cell (iPSC) line was successfully created from a male patient with hypoplastic left heart syndrome (HLHS), which can be used to study the disease's cellular and developmental causes.

The iPSC line demonstrated normal characteristics, including morphology, pluripotency marker expression, and the ability to differentiate into various cell types, indicating its potential for research in HLHS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of an iPSC line NCHi006-A from a patient with hypoplastic left heart syndrome (HLHS). Alonzo, M., Contreras, J., Ye, S., et al.[2022]

Hypoplastic left heart syndrome (HLHS) is a critical heart condition that often leads to rapid deterioration in infants, with a mortality rate of 55% observed in a study of 40 patients aged 1 to 120 days.

Palliative surgeries, such as the Norwood technique, can provide immediate benefits, but the success of these interventions heavily relies on early diagnosis and timely clinical management, as complications like infections can lead to significant postoperative mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypoplastic left heart syndrome. Clinical evaluation of 40 patients]. Bhering, MA., Atik, E., Iwahashi, ER., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Potential Role of Regenerative Medicine on the Future Management of Hypoplastic Left Heart Syndrome. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Intramyocardial Bone Marrow Stem Cells in Patients Undergoing Cardiac Surgical Revascularization. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Autologous bone marrow mesenchymal cell transplantation improves left ventricular function in a rabbit model of dilated cardiomyopathy. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). [2022]

7. England pubmed.ncbi.nlm.nih.gov

Establishment of NCHi009-A, an iPSC line from a patient with hypoplastic left heart syndrome (HLHS) carrying a heterozygous NOTCH1 mutation. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Characterization of an iPSC line NCHi006-A from a patient with hypoplastic left heart syndrome (HLHS). [2022]

10. Brazil pubmed.ncbi.nlm.nih.gov

[Hypoplastic left heart syndrome. Clinical evaluation of 40 patients]. [2016]