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

Phase 1

Recruiting

• Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy
• Interventions: Genetic: TN-401

• Registration Number: NCT06228924
• Lead Sponsor: Tenaya Therapeutics

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.

Study Timeline

• Study First Submitted: 2024-01-18
• Study First Submitted QC: 2024-01-18
• Study First Posted: 2024-01-29
• Study Start: 2024-03-26
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2026-05-01
• Study Completion: 2029-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	TN-401	Dose for Cohort 1 will be 3E13 vg/kg
Cohort 2	TN-401	Dose for Cohort 2 will be 6E13 vg/kg

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

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

Trial Locations

Locations (7)

University of California San Francisco; 🇺🇸 San Francisco, California, 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

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States