Lomecel-B for Hypoplastic Left Heart Syndrome

(ELPIS Trial)

Not currently recruiting at 4 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Longeveron Inc.

Must not be taking: Anti-arrhythmia therapy

Disqualifiers: Arrhythmia, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Lomecel-B (mesenchymal stem cells) to determine its safety and effectiveness for children with Hypoplastic Left Heart Syndrome (HLHS), a serious heart condition. The treatment is administered during standard heart surgery through injections directly into the heart muscle. Participants are divided into two groups: one receives the Lomecel-B treatment, while the other does not, allowing for comparison of results. This trial may suit children needing a specific heart surgery (BDCPA) for HLHS and not experiencing certain additional heart problems. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works and measure its effectiveness in an initial, smaller group of children.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on anti-arrhythmia therapy, you may not be eligible to participate.

Is there any evidence suggesting that Lomecel-B is likely to be safe for humans?

Research has shown that Lomecel-B is generally safe for individuals with hypoplastic left heart syndrome (HLHS). Previous studies found that patients tolerated the treatment well, with no major safety issues reported. For instance, one study found that injecting Lomecel-B into the heart muscle did not cause serious side effects and might even improve heart function. Another study confirmed that this treatment was safe and practical for HLHS patients undergoing heart surgery.

These findings suggest that Lomecel-B is likely safe for those considering participation in a clinical trial. However, as with any medical treatment, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for HLHS?

Researchers are excited about Lomecel-B for Hypoplastic Left Heart Syndrome (HLHS) because it utilizes Longeveron Mesenchymal Stem Cells (LMSCs), which is a new approach compared to traditional surgical methods. Unlike conventional treatments that focus mainly on surgical reconstruction of the heart, Lomecel-B involves injecting these stem cells directly into the heart muscle during surgery. This unique mechanism aims to enhance heart function and improve outcomes by promoting tissue repair and regeneration. The use of stem cells to potentially improve heart health represents a promising advancement that could complement existing surgical interventions.

What evidence suggests that Lomecel-B might be an effective treatment for Hypoplastic Left Heart Syndrome?

Research has shown that Lomecel-B, a type of cell-based therapy, could help treat hypoplastic left heart syndrome (HLHS). In this trial, some participants will receive Lomecel-B during surgery, while others will not receive any cells or injections. Earlier studies found that patients who received Lomecel-B during surgery experienced better heart function, and the treatment was safe. It may specifically enhance the function of the right side of the heart, which is crucial for individuals with HLHS. Early results also suggest that Lomecel-B is safe when injected directly into the heart muscle during surgery. These findings offer hope that Lomecel-B might improve heart performance in children with HLHS. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for patients with Hypoplastic Left Heart Syndrome (HLHS) who need stage II surgery. It's not for those with certain HLHS complications, positive tests for HIV/HBV/HCV, chromosomal abnormalities, arrhythmias needing treatment, or additional heart issues requiring other surgeries.

Inclusion Criteria

I have HLHS and need BDCPA surgery.

Exclusion Criteria

My cancer has specific genetic changes.

I have large blood vessels in my heart's artery.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Stage I

10 HLHS patients in Cohort A receive Lomecel-B via intramyocardial injections during Stage II surgery. Initial 3 patients evaluated for 5 days for safety.

5 days

In-hospital stay for surgery and initial evaluation

Safety Review

Formal safety review conducted 6 months post-treatment of the last patient in Cohort A.

6 months

Treatment - Stage II

20 HLHS patients randomized in a double-blind manner to receive Lomecel-B or no treatment during Stage II surgery.

During surgery

In-hospital stay for surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiac function and somatic growth assessments.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lomecel-B

Trial Overview The study evaluates the safety and potential benefits of Lomecel-B stem cells given as an extra treatment during standard stage II surgery for HLHS. The cells are injected directly into the heart muscle.

How Is the Trial Designed?

Group I: Cohort B - Phase 2 Treatment Group Experimental Treatment 1 Intervention

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.

Group II: Cohort A - Phase 1 (Open Label) Experimental Treatment 1 Intervention

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.

Group III: Cohort C - Phase 2 Control Group Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Longeveron Inc.

Lead Sponsor

Trials

10

Recruited

480+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04925024

Study Details | NCT04925024 | Evaluation of Lomecel-B™ ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10026620/

Intramyocardial cell-based therapy with Lomecel-B during ... Here we present the results of the phase I ELPIS trial (Allogeneic Human Mesenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: A P ...

3. investors.longeveron.com investors.longeveron.com/news/News/news-details/2021/Longeveron-Announces-Final-Results-of-Phase-1-Clinical-Study-of-Lomecel-B-Injection-in-Hypoplastic-Left-Heart-Syndrome-Patients/default.aspx

News Details Longeveron Announces Final Results of Phase 1 Clinical Study of Lomecel-B Injection in Hypoplastic Left Heart Syndrome Patients. 09/09/2021. --Study meets ...

4. investors.longeveron.com investors.longeveron.com/news/News/news-details/2024/Longeveron-Presents-Lomecel-B-Long-term-Transplant-free-Survival-Data-in-Hypoplastic-Left-Heart-Syndrome-HLHS-at-the-Congenital-Heart-Surgeons-Society-CHSS-51st-Annual-Meeting/default.aspx

Longeveron® Presents Lomecel-B™ Long-term Transplant ... Longeveron is currently pursuing three pipeline indications: hypoplastic left heart syndrome (HLHS), Alzheimer's disease (AD), and Aging-related ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36950450/

Intramyocardial cell-based therapy with Lomecel-B during ... Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666273623003042

Hypoplastic Left Heart Syndrome Prospective randomized ... A novel mesenchymal precursor cell therapy was safe and feasible in pediatric patients with HLHS undergoing staged LV recruitment surgery.