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

Arrhythmogenic Right Ventricular Cardiomyopathy Clinical Trial

— RIDGE-1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06228924
• Other study ID #: TN-401-0012
• Status: Recruiting
• Phase: Phase 1
• Start date: March 26, 2024
• Est. completion date: October 1, 2029

Study information

• Verified date: May 2024
• Source: Tenaya Therapeutics
• Contact: Matthew Pollman, M.D.
• Phone: (650) 416-1186
• Email: mpollman[@]tenayathera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: October 1, 2029
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmogenic Right Ventricular Cardiomyopathy
• Arrhythmogenic Right Ventricular Dysplasia
• Cardiomyopathies

Intervention

Genetic:
• TN-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.

Locations

Country	Name	City	State
United States	University of Colorado - Anschutz Medical Campus	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	NYU Langone Health	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Tenaya Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and severity of Adverse Events over the course of the study.		52 weeks
Primary	Number of Serious Adverse Events related to study drug.		5 years
Secondary	To assess changes in daily PVC and NSVT counts		Week 52
Secondary	To assess frequency of ICD therapy administration		Week 52
Secondary	To assess frequency of sustained VT		Week 52

External Links

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