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

NCT06228924 · Tenaya Therapeutics
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Official title
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)
About this study
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
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
Study design
Enrollment target: 15 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-03-26
Estimated completion: 2029-10-01
Last updated: 2025-02-06
Interventions
Genetic: TN-401
Primary outcomes
  • Number and severity of Adverse Events over the course of the study. (52 weeks)
  • Number of Serious Adverse Events related to study drug. (5 years)
Sponsor
Tenaya Therapeutics · industry
Contacts & investigators
ContactMatthew Pollman, M.D. · contact · mpollman@tenayathera.com · (650) 416-1186
ContactNiha Kamat · contact · clinical.trials@tenayathera.com
All locations (7)
University of California San FranciscoRecruiting
San Francisco, California, United States
University of Colorado - Anschutz Medical CampusRecruiting
Aurora, Colorado, United States
Johns Hopkins UniversityRecruiting
Baltimore, Maryland, United States
Brigham and Women's HospitalRecruiting
Boston, Massachusetts, United States
Mayo ClinicRecruiting
Rochester, Minnesota, United States
NYU Langone HealthRecruiting
New York, New York, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC · TrialPath