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NCT06228924PHASE1Recruiting

Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC

Tenaya Therapeutics

Start Date

3/26/2024

Completion Date

10/1/2029

Summary

This first-in-human study is designed to evaluate the safety, and preliminary efficacy (PD) of TN-401 gene therapy in adult patients with symptomatic PKP2 mutation-associated ARVC.

Detailed Description

The RIDGE-1™ open-label Safety, Tolerability, Dose-finding, PD and Cardiac Transgene Expression Study will enroll up to 15 patients in two planned dose cohorts. Patients in each cohort will receive a single intravenous (IV) dose of TN-401. Following Data Safety Monitoring Board (DSMB) review of each dose cohort, the next dose cohort will be initiated. DSMB review will also be needed to expand the dose cohorts. The dose for Cohorts 1/1a will be 3E13 (3 × 1013) vg/kg and the dose for Cohorts 2/2a will be 6E13 (6 × 1013) vg/kg.

Eligibility Criteria

Age Range: 18 years to 65 years

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

Interventions

GENETIC

TN-401

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Conditions

Arrhythmogenic Right Ventricular Cardiomyopathy

Locations

University of California San Francisco

San Francisco, California 94143

United States

University of Colorado - Anschutz Medical Campus

Aurora, Colorado 80045

United States

Johns Hopkins University

Baltimore, Maryland 21287

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

NYU Langone Health

New York, New York 10016

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States