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

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)

Status

Recruiting

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06228924

Acronym

RIDGE-1

Enrollment

Registered

2024-01-29

Start date

2024-03-26

Completion date

2029-10-01

Last updated

2025-02-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arrhythmogenic Right Ventricular Cardiomyopathy

Keywords

PKP2 Mutation Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Arrhythmogenic Cardiomyopathy (ACM), PKP2-associated ARVC, PKP2-ARVC, PKP2-ACM, Adeno Associated Virus (AAV), Gene Therapy, Gene Transfer, Genetic cardiomyopathy, Heart Failure

Brief 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.

Interventions

GENETICTN-401

TN-401 is a recombinant adeno-associated virus serotype 9 (AAV9) gene therapy containing Plakophilin-2 (PKP2) transgene. It is a single (one-time) intravenous dose.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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

Secondary

Measure	Time frame
To assess changes in daily PVC and NSVT counts	Week 52
To assess frequency of ICD therapy administration	Week 52
To assess frequency of sustained VT	Week 52

Countries

United States

Contacts

Primary ContactMatthew Pollman, M.D.

mpollman@tenayathera.com(650) 416-1186

Backup ContactNiha Kamat

clinical.trials@tenayathera.com

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026