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

February 5, 2025 updated by: Tenaya Therapeutics

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Contact:
          • Vasanth Vedantham, MD
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado - Anschutz Medical Campus
        • Contact:
          • Matthew Taylor, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University
        • Contact:
          • Andreas Barth, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
          • Neal Lakdawala, MD
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
          • John R. Giudicessi, MD
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Health
        • Contact:
          • Larry Chinitz, MD
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
          • Milind Desai, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number and severity of Adverse Events over the course of the study.
Time Frame: 52 weeks
52 weeks
Number of Serious Adverse Events related to study drug.
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess changes in daily PVC and NSVT counts
Time Frame: Week 52
Week 52
To assess frequency of ICD therapy administration
Time Frame: Week 52
Week 52
To assess frequency of sustained VT
Time Frame: Week 52
Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tenaya Therapeutics

Collaborators

Johns Hopkins University
Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2024

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

October 1, 2029

Study Registration Dates

First Submitted

January 18, 2024

First Submitted That Met QC Criteria

January 18, 2024

First Posted (Actual)

January 29, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 5, 2025

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TN-401-0012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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