iPSC-CL for Congenital Heart Disease

Overseen By Adam Armstrong

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: HeartWorks, Inc.

Must not be taking: Amiodarone

Disqualifiers: Coronary artery disease, Cancer, Obesity, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of using lab-grown heart cells made from stem cells, known as iPSC-CL (Autologous Induced Pluripotent Stem Cells of Cardiac Lineage), to assist individuals with congenital heart disease, a condition present at birth that affects the heart's structure. Researchers aim to determine if these cells are safe for human use and if conducting this trial is feasible. Participants will either receive a dose of the treatment or join a control group for comparison. The trial seeks individuals with severe heart failure due to congenital heart disease who have not found success with other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that all guideline-directed therapy should be maximized for at least 3 months before enrollment, which suggests you may need to continue your current treatments.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that lab-grown heart cells made from stem cells, known as iPSC-CL, hold promise in safety tests. Tests in animals have demonstrated improved heart function without major side effects. In human trials, the focus remains on safety, and these cells have been well-tolerated so far.

As a Phase 1 trial, the primary goal is to ensure the treatment's safety. Researchers closely monitor for any negative effects. Early studies in animals and humans have not reported major safety issues. However, since this is an initial step in human testing, ongoing monitoring is crucial to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about iPSC-CL for congenital heart disease because it uses induced pluripotent stem cells (iPSCs) to potentially repair or regenerate damaged heart tissue. Unlike traditional treatments, which often involve surgery or medication to manage symptoms, iPSC-CL works at a cellular level to address the root cause. This innovative approach could lead to long-term improvements in heart function, offering hope for more effective and less invasive solutions for patients with congenital heart disease.

What evidence suggests that iPSC-CL might be an effective treatment for congenital heart disease?

Research has shown that lab-grown heart cells made from stem cells, known as iPSC-CL, could improve heart function. In animal studies, transplanting these cells led to better heart performance. The science involves reverting ordinary cells to a more flexible state, allowing them to become heart cells. This process, called induction, suggests potential for repairing damaged heart tissue. In this trial, participants in the treated arm will receive one dose of the investigational product, iPSC-CL, at varying dose levels. Although human trials remain in the early stages, animal results are promising for treating conditions like congenital heart disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Timothy J Nelson, M.D., Ph.D.

Principal Investigator

HeartWorks, Inc.

Are You a Good Fit for This Trial?

This trial is for adults aged 18-40 with single ventricle congenital heart disease, class IV heart failure, and an ejection fraction below 40%. They must have maximized all treatments, be ineligible or waiting for a heart transplant, possibly on mechanical support, and able to consent. Exclusions include substance abuse, active infections, uncontrolled depression or other conditions that could risk safety or compliance.

Inclusion Criteria

I understand the study and can give my consent.

I have a heart condition where I was born with only one ventricle.

I am on the US heart transplant list but may not receive a heart in time.

Exclusion Criteria

You are currently struggling with alcohol or drug abuse, which could prevent you from getting a heart transplant.

I have had cancer in the past.

Past or current medical problems or findings from physical examination or laboratory testing that may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality of the data obtained from the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one dose of Investigational Product with dose levels escalating based on treatment date

1 day

1 visit (in-person)

Short-term Follow-up

Participants are monitored for short-term safety, defined as the rate of new or worsening serious adverse events within 3 months of iPSC-CL delivery

3 months

Long-term Follow-up

Participants are monitored for long-term safety and changes in various biomarkers, with assessments up to 15 years

15 years

What Are the Treatments Tested in This Trial?

Interventions

• iPSC-CL

Trial Overview The trial tests the safety of lab-grown heart cells (iPSC-CL) in those with congenital heart disease. Participants will receive these cells and undergo monitoring before and after treatment to assess safety and feasibility. The study includes lifelong follow-up comparing treated subjects against untreated ones from the same pool.

How Is the Trial Designed?

Group I: Treated Experimental Treatment 1 Intervention

Subjects in Treated arm will receive one dose of Investigational Product. Within this arm are three dose levels. Dose level selection will be determined by product availability subjects have available product and when they can be treated. Dose levels will escalate in order of treatment date.

Group II: Control Active Control 1 Intervention

Subjects who enroll but do not receive Investigational Product will be placed in the control arm.

Who Is Running the Clinical Trial?

HeartWorks, Inc.

Lead Sponsor

Trials

3

Recruited

650+

Published Research Related to This Trial

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes can significantly enhance our understanding of congenital heart disease (CHD) by modeling its development and identifying potential therapeutic targets.

These hiPSC-derived models allow for personalized research, enabling the investigation of disease-specific mechanisms and the exploration of novel therapies for CHD, which is crucial given the unknown etiology of most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model for Heart Development and Congenital Heart Disease. Doyle, MJ., Lohr, JL., Chapman, CS., et al.[2022]

Induced pluripotent stem cells (iPSCs) derived from patients with single ventricle defects (SVD) allow researchers to study the disease in patient-specific cardiomyocytes, which can help uncover the genetic and cellular causes of SVD.

Recent advancements in iPSC technology, including the creation of 3D organoids and chamber-specific cardiac cells, provide new insights into the mechanisms of SVD development and offer a platform for testing potential therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced Pluripotent Stem Cell-Based Modeling of Single-Ventricle Congenital Heart Diseases. Parker, LE., Kurzlechner, LM., Landstrom, AP.[2023]

Induced pluripotent stem cells (iPSCs) can be efficiently generated without inserting foreign genes, allowing them to differentiate into various cell types, including cardiac myocytes, which are crucial for heart research.

iPSC-derived cardiac myocytes are valuable for modeling human diseases, testing drugs, and assessing patient responses, as they reflect genetic variations and can also be used for cardiac regeneration in animal studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced Pluripotent Stem Cells 10 Years Later: For Cardiac Applications. Yoshida, Y., Yamanaka, S.[2022]

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) can effectively detect chronic cardiac risks from drugs, showing changes in contractile motion and increased release of cardiac biomarkers over a 72-hour exposure to cardiotoxic drugs.

Specific biomarkers like cardiac troponin I (cTnI) and heart fatty acid binding protein (FABP3) were identified as reliable indicators of cardiotoxicity, suggesting that hiPS-CMs could enhance the safety assessment of new drugs earlier in the development process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic drug-induced effects on contractile motion properties and cardiac biomarkers in human induced pluripotent stem cell-derived cardiomyocytes. Kopljar, I., De Bondt, A., Vinken, P., et al.[2022]

Induced pluripotent stem (iPS) cells derived from a patient with a ventricular septal defect (VSD) were successfully generated and shown to have the potential to differentiate into functional heart cells, providing a new model for studying VSD.

The study confirmed the self-renewal and pluripotency of these VSD-iPS cells, which can help researchers understand the origins and mechanisms of VSD, potentially leading to better treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymic derived iPs cells can be differentiated into cardiomyocytes. Li, J., Cao, YY., Ma, XJ., et al.[2022]

Human induced pluripotent stem cells (hiPSCs) are being used to model congenital heart disease (CHD), providing insights into the molecular mechanisms of cardiac development and the pathogenesis of various CHD subtypes.

hiPSC technology holds promise for personalized medicine in CHD, enabling patient-specific modeling, drug screening, and potentially leading to novel preventative therapies, although challenges like reproducibility and cellular heterogeneity remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational potential of hiPSCs in predictive modeling of heart development and disease. Mansfield, C., Zhao, MT., Basu, M.[2023]

Induced pluripotent stem cells (iPSCs) are promising for developing disease models and therapies for cardiac disorders, with recent advancements in protocols allowing for the efficient generation of high-quality cardiac myocytes.

New genome-editing techniques enable targeted manipulation of patient-specific iPSCs, facilitating the creation of isogenic lines for better disease modeling and clinical-grade lines for potential replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generating patient-specific induced pluripotent stem cells-derived cardiomyocytes for the treatment of cardiac diseases. Jeziorowska, D., Korniat, A., Salem, JE., et al.[2018]

Induced pluripotent stem cells (iPSCs) allow researchers to create patient-specific models for studying diseases, particularly in cardiology, which can lead to advancements in drug discovery and personalized medicine.

Challenges remain in developing effective protocols for maturation of iPSC-derived cardiac cells and ensuring the safety and efficiency of these cells for future therapies, especially in pediatric populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells in pediatric cardiology. Patel, P., Mital, S.[2021]

A new induced pluripotent stem cell (iPSC) line, NCHi001-A, was successfully created from Epstein-Barr virus (EBV) immortalized lymphoblastoid cell lines (LCLs) of a patient with congenital aortic valve stenosis, demonstrating the potential of LCLs for generating iPSCs.

NCHi001-A is free from EBV and transgenes, shows normal stem cell characteristics, and can differentiate into various cell types, making it a valuable resource for modeling congenital heart disease, drug discovery, and developing cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation and characterization of a human induced pluripotent stem cell (iPSC) line from a patient with congenital heart disease (CHD). Lin, H., Ye, SQ., Xu, ZH., et al.[2023]

The study identified that using standardized gene expression profiles can help select induced pluripotent stem cell (iPSC) clones that minimize the influence of their somatic origin on differentiation, leading to more predictable outcomes in regenerative medicine.

Doxycycline-induced iPSCs showed faster differentiation into cardiac tissue compared to lentiviral-reprogrammed lines, indicating that the reprogramming strategy significantly affects the efficiency of tissue specification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection via pluripotency-related transcriptional screen minimizes the influence of somatic origin on iPSC differentiation propensity. Hartjes, KA., Li, X., Martinez-Fernandez, A., et al.[2022]

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Autologous Induced Pluripotent Stem Cells of Cardiac ... The goal of this clinical trial is to test the safety of lab-grown heart cells made from stem cells in subjects with congenital heart disease.