Gene Therapy for Arrhythmogenic Cardiomyopathy

Recruiting at 4 trial locations

Overseen By LEXEO Clinical Trials

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Lexeo Therapeutics

Disqualifiers: Other cardiac abnormalities, NYHA Class IV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase 1/2, first-in-human, open-label, intravenous, dose-escalating, multicenter trial that is designed to assess the safety and tolerability of LX2020 in adult patients with PKP2-ACM

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment LX2020 for arrhythmogenic cardiomyopathy?

Gene therapies have shown promise in treating inherited arrhythmias, which are similar to arrhythmogenic cardiomyopathy, by targeting specific genetic mutations that cause these heart rhythm problems. This suggests that LX2020, as a gene therapy, might also be effective in addressing the genetic causes of arrhythmogenic cardiomyopathy. ^{1 2 3 4 5}

How is the treatment LX2020 different from other treatments for arrhythmogenic cardiomyopathy?

LX2020 is a gene therapy specifically targeting the genetic mutations associated with arrhythmogenic cardiomyopathy, which is unique compared to other treatments that may not address the underlying genetic causes of the disease. ^{1 4 5 6 7}

Research Team

LEXEO Clinical Trials

Principal Investigator

Lexeo Therapeutics

Eligibility Criteria

This trial is for adults with a specific heart condition called Arrhythmogenic Cardiomyopathy (ACM) due to a PKP2 gene variant. Participants must meet certain diagnostic criteria, have frequent irregular heartbeats known as PVCs, and have had an ICD (a device that can prevent sudden death from cardiac arrest) implanted for at least 12 weeks. They should also have a left ventricular ejection fraction of 50% or higher.

Inclusion Criteria

Frequent premature ventricular complexes (PVCs)

I have been diagnosed with ACM according to the 2010 criteria.

Left ventricular ejection fraction ≥ 50%

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single ascending dose of LX2020 in multiple cohorts

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• LX2020 (Virus Therapy)

Trial Overview The trial is testing LX2020, which is a new gene therapy given through the veins. It's in early stages of testing (Phase 1/2), where researchers are trying to find out how safe it is and what doses are tolerable when given to humans for the first time.

Participant Groups

Group I: LX2020 Experimental Treatment 1 Intervention

Single ascending dose of LX2020, with a starting dose of 2.0 x10\^13 gc/kg, in multiple cohorts

Who Is Running the Clinical Trial?

Lexeo Therapeutics

Lead Sponsor

Trials

5

Recruited

110+

Findings from Research

In a study of 168 patients with arrhythmogenic cardiomyopathy (AC), greater exercise exposure was linked to worse left ventricular (LV) function at the initial assessment, indicating that exercise may exacerbate LV dysfunction in these patients.

The progression of LV dysfunction over time was most significant in patients with the desmoplakin genotype, and this deterioration was a predictor of future ventricular tachyarrhythmias, highlighting the importance of monitoring LV function for risk assessment in AC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Ventricular Dysfunction in Arrhythmogenic Cardiomyopathy: Association With Exercise Exposure, Genetic Basis, and Prognosis. Lie, ØH., Chivulescu, M., Rootwelt-Norberg, C., et al.[2021]

Arrhythmogenic cardiomyopathy primarily affects young males, with a median diagnosis age of 38.2 years, and all patients experienced potentially fatal ventricular arrhythmias, highlighting the condition's serious nature.

Among the 13 patients studied, 84.6% are still alive, with treatment strategies including implantable cardioverter defibrillators (ICDs) for secondary prevention, ablation, and heart transplantation, indicating effective management options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical profile and therapeutic strategies in patients with arrhythmogenic cardiomyopathy treated in a national reference institute]. Huerta Robles, R., Chávez Solsol, F., Muñoz Moreno, J., et al.[2023]

Inherited arrhythmias, caused by genetic mutations, pose a lifelong risk of sudden death and are linked to various conditions like long QT syndrome and hypertrophic cardiomyopathy.

Recent studies indicate that gene therapies may offer targeted treatment options for certain inherited arrhythmias, potentially improving outcomes where current therapies fall short.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for inherited arrhythmias. Bezzerides, VJ., Prondzynski, M., Carrier, L., et al.[2021]

Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease that leads to dangerous heart rhythms and can result in sudden cardiac death, with its genetic basis becoming clearer due to advancements in genetic analysis techniques.

Various preclinical models, including gene-targeted animals and human stem cell-derived heart cells, are being used to better understand ACM's mechanisms and the relationship between specific genetic mutations and disease outcomes, which could help improve patient prognosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology. Fan, X., Yang, G., Duru, F., et al.[2023]

Arrhythmogenic cardiomyopathy, though rare, is primarily caused by single-gene mutations affecting desmosomal proteins, which are crucial for cell adhesion and mechanical stability in heart tissue.

Understanding the mechanisms behind the arrhythmogenic features of this disease could provide insights into lethal heart rhythms and sudden cardiac death in more prevalent heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pathobiology of arrhythmogenic cardiomyopathy. Saffitz, JE.[2012]

Arrhythmogenic cardiomyopathy (AC) is linked to mutations in desmosomal proteins in about 50% of patients, highlighting the genetic basis of the disease.

Recent research indicates that changes in intercalated disk proteins and abnormal cell signaling pathways play a significant role in the development of AC, suggesting potential targets for future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remodeling of cell-cell junctions in arrhythmogenic cardiomyopathy. Asimaki, A., Saffitz, JE.[2021]

Arrhythmogenic cardiomyopathy (AC) is a serious heart condition that can lead to dangerous heart rhythms and sudden cardiac death, particularly in young athletes, and is characterized by scarring in the heart muscle.

The disease has a genetic basis linked to mutations in cardiac desmosome genes, but also includes non-genetic factors, leading to a variety of symptoms and disease progression that varies with age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural History of Arrhythmogenic Cardiomyopathy. Mattesi, G., Zorzi, A., Corrado, D., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Left Ventricular Dysfunction in Arrhythmogenic Cardiomyopathy: Association With Exercise Exposure, Genetic Basis, and Prognosis. [2021]

2. Peru pubmed.ncbi.nlm.nih.gov

[Clinical profile and therapeutic strategies in patients with arrhythmogenic cardiomyopathy treated in a national reference institute]. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Gene therapy for inherited arrhythmias. [2021]

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

Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology. [2023]

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

The pathobiology of arrhythmogenic cardiomyopathy. [2012]

6. England pubmed.ncbi.nlm.nih.gov

Remodeling of cell-cell junctions in arrhythmogenic cardiomyopathy. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Natural History of Arrhythmogenic Cardiomyopathy. [2020]