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

NCT ID: NCT06228924

Last Updated: 2025-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-26

Study Completion Date

2029-10-01

Brief Summary

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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

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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.

Conditions

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Arrhythmogenic Right Ventricular Cardiomyopathy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

Dose for Cohort 1 will be 3E13 vg/kg

Group Type EXPERIMENTAL

TN-401

Intervention Type GENETIC

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.

Cohort 2

Dose for Cohort 2 will be 6E13 vg/kg

Group Type EXPERIMENTAL

TN-401

Intervention Type GENETIC

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.

Interventions

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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.

Intervention Type GENETIC

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tenaya Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Matthew Pollman, M.D.

Role: CONTACT

(650) 416-1186

Niha Kamat

Role: CONTACT

Facility Contacts

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Vasanth Vedantham, MD

Role: primary

Matthew Taylor, MD

Role: primary

Neal Lakdawala, MD

Role: primary

Larry Chinitz, MD

Role: primary

Milind Desai, MD

Role: primary

Other Identifiers

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TN-401-0012

Identifier Type: -

Identifier Source: org_study_id

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