Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1
Dose for Cohort 1 will be 3E13 vg/kg
  • 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.
Experimental
Cohort 2
Dose for Cohort 2 will be 6E13 vg/kg
  • 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.

Recruiting Locations

Brigham and Women's Hospital
Boston, Massachusetts 02115
Contact:
Neal Lakdawala, MD

More Details

Status
Recruiting
Sponsor
Tenaya Therapeutics

Study Contact

Matthew Pollman, M.D.
(650) 416-1186
mpollman@tenayathera.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.