Clinical trial NCT06228924: Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Tenaya Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-01-29
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number and severity of Adverse Events over the course of the study.
timeFrame: 52 weeks
measure: Number of Serious Adverse Events related to study drug.
timeFrame: 5 years
Secondary outcomes:
measure: To assess changes in daily PVC and NSVT counts
timeFrame: Week 52
measure: To assess frequency of ICD therapy administration
timeFrame: Week 52
measure: To assess frequency of sustained VT
timeFrame: Week 52
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado - Anschutz Medical Campus
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
References: