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

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.

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