Actively Recruiting

Phase 1
Age: 18Years - 65Years
All Genders
ID06228924

First-in-Human Study of TN-401 Gene Therapy for Adults With PKP2 Mutation-Associated Arrhythmogenic Right Ventricular Cardiomyopathy Evaluating Safety and Preliminary Effects

Led by Tenaya Therapeutics · Updated on 2025-02-06

15

Participants Needed

7

Research Sites

178 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and early effects of TN-401 gene therapy in adults with symptomatic arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by PKP2 gene mutations. This first-in-human study focuses on how well this gene therapy is tolerated and its preliminary impact on the condition. The study is in its initial phase and aims to understand both safety and gene expression in the heart. Participants are divided into two groups receiving different doses of TN-401, a one-time intravenous gene therapy using a recombinant adeno-associated virus containing the PKP2 gene. The first group receives a dose of 3 x 10^13 vector genomes per kilogram, and the second group receives 6 x 10^13 vector genomes per kilogram. After safety reviews by an independent board, dosing for each group may be expanded. During the study, participants will be monitored for side effects and serious adverse events over one to five years. Researchers will track daily heart rhythm irregularities, frequency of implantable defibrillator therapies, and sustained ventricular tachycardia episodes over 52 weeks. The study involves regular assessments to check heart function, device performance, and gene therapy effects, ensuring close safety and treatment monitoring throughout the participation period.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years - 65Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Documented PKP2 mutation classified as pathogenic or likely pathogenic
  • Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy meeting the 2010 revised Task Force Criteria
  • Left Ventricular Ejection Fraction of 50% or higher
  • Functioning implantable cardiac defibrillator with remote monitoring for at least 9 months before screening
  • New York Heart Association (NYHA) Functional Class I, II, or III
  • Presence of frequent premature ventricular contractions (PVCs)
Not Eligible

You will not qualify if you...

  • Ventricular tachycardia (VT) ablation performed within 6 months before screening or planned within 6 months after screening
  • High neutralizing antibody levels against AAV9
  • History of prior myocardial infarction
  • Diagnosis of right ventricular heart failure
  • New York Heart Association (NYHA) Class IV heart failure
  • Clinically significant kidney disease
  • Clinically significant liver disease

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 1 day

Participants receive a single intravenous dose of TN-401 gene therapy to assess safety and preliminary efficacy.

1 dosing visit (in-person)

Follow-up

Duration - Up to 5 years

Participants are monitored for safety, adverse events, and preliminary treatment effects over an extended period.

Regular visits during first year with additional long-term safety monitoring visits

Trial Site Locations

Total: 7 locations

1

University of California San Francisco

San Francisco, California, United States, 94143

Actively Recruiting

2

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, United States, 80045

Actively Recruiting

3

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Actively Recruiting

4

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Actively Recruiting

5

Mayo Clinic

Rochester, Minnesota, United States, 55905

Actively Recruiting

6

NYU Langone Health

New York, New York, United States, 10016

Actively Recruiting

7

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Actively Recruiting

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Research Team

M

Matthew Pollman, M.D.

N

Niha Kamat

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

2

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