Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC (RIDGE-1)

Tenaya Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy

Treatments: Genetic: TN-401

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06228924

TN-401-0012

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

15 participants in 2 patient groups

Cohort 1

Experimental group

Description:

Dose for Cohort 1 will be 3E13 vg/kg

Treatment:

Genetic: TN-401

Cohort 2

Experimental group

Description:

Dose for Cohort 2 will be 6E13 vg/kg

Treatment:

Genetic: TN-401