Gene therapy for adults with PKP2 mutation-associated heart disease

First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-401, a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Containing Plakophilin-2 (PKP2) Transgene, in Adults With PKP2 Mutation-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

This study is testing a new gene therapy called TN-401 to see if it can help adults with heart disease caused by a specific genetic mutation feel better and stay safe.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Tenaya Therapeutics (industry)
• Locations: 7 sites (San Francisco, California and 6 other locations)
• Trial ID: NCT06228924 on ClinicalTrials.gov

What this trial studies

This open-label, dose escalation study aims to evaluate the safety and preliminary efficacy of TN-401 gene therapy in adults suffering from symptomatic PKP2 mutation-associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). The study will enroll up to 15 patients, who will receive a single intravenous dose of TN-401 in two planned dose cohorts. Following a review by the Data Safety Monitoring Board (DSMB), the next dose cohort will be initiated, allowing for careful monitoring of safety and efficacy as the study progresses.

Who should consider this trial

Good fit: Ideal candidates for this study are adults with a confirmed PKP2 mutation and symptomatic ARVC who meet specific cardiac function criteria.

Not a fit: Patients with advanced heart failure, recent ventricular tachycardia ablation, or significant renal or liver disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option for patients with PKP2 mutation-associated ARVC, potentially improving their heart function and quality of life.

How similar studies have performed: While gene therapy approaches are emerging, this specific application for PKP2 mutation-associated ARVC is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* PKP2 mutation (pathogenic or likely pathogenic)
* Arrhythmogenic Right Ventricular Cardiomyopathy as defined by the 2010 revised Task Force Criteria
* Left Ventricular Ejection Fraction ≥50%
* Functioning Implantable Cardiac Defibrillator with remote integration capabilities at least 9 months prior to Screening
* NYHA Functional Class I, II, or III
* Frequent premature ventricular contractions (PVCs)

Exclusion Criteria:

* Ventricular tachycardia (VT) ablation within 6 months of Screening or planned VT ablation within 6 months after Screening
* High AAV9 neutralizing antibody titer
* Prior myocardial infarction
* Right Ventricular Heart Failure
* Class IV Heart Failure
* Clinically significant renal disease
* Clinically significant liver disease

Where this trial is running

San Francisco, California and 6 other locations

• University of California San Francisco — San Francisco, California, United States (RECRUITING)
• University of Colorado - Anschutz Medical Campus — Aurora, Colorado, United States (RECRUITING)
• Johns Hopkins University — Baltimore, Maryland, United States (RECRUITING)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)
• NYU Langone Health — New York, New York, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Study coordinator: Matthew Pollman, M.D.

Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy, PKP2 Mutation Arrhythmogenic Right Ventricular Cardiomyopathy, Arrhythmogenic Cardiomyopathy, PKP2-associated ARVC, PKP2-ARVC, PKP2-ACM, Adeno Associated Virus, Gene Therapy