Arrhythmogenic Right Ventricular CardiomyopathyPhase 1RIDGE-1NCT06228924
Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC
A Phase 1 study testing TN-401 in people with Arrhythmogenic Right Ventricular Cardiomyopathy, run by Tenaya Therapeutics at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Arrhythmogenic Right Ventricular Cardiomyopathy
- What is being tested?
- TN-401
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 7 sitesUnited States
- Study dates
- 26 Mar 2024to 1 Oct 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Niha Kamat contact
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
University of Colorado - Anschutz Medical Campus
Aurora, Colorado, 80045
Matthew Taylor, MD
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Andreas Barth, MD
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Neal Lakdawala, MD
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Milind Desai, MD
- Recruiting
NYU Langone Health
New York, New York, 10016
Larry Chinitz, MD
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
John R. Giudicessi, MD
- Recruiting
University of California San Francisco
San Francisco, California, 94143
Vasanth Vedantham, MD
About this study
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)
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.
Read the 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.
- Being tested
- TN-401
- 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
- Medical subject headings
- Arrhythmogenic Right Ventricular Dysplasia, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TN-401Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Dose for Cohort 1 will be 3E13 vg/kg Receives: Genetic: TN-401 |
| Cohort 2 | Experimental | Dose for Cohort 2 will be 6E13 vg/kg Receives: Genetic: TN-401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of Adverse Events over the course of the study.
Measured: 52 weeks
Number of Serious Adverse Events related to study drug.
Measured: 5 years
Secondary outcomes (3)
To assess changes in daily PVC and NSVT counts
Measured: Week 52
To assess frequency of ICD therapy administration
Measured: Week 52
To assess frequency of sustained VT
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2024
- Study start26 Mar 2024
- Primary completion1 May 2026 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arrhythmogenic Right Ventricular CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tenaya Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06228924
- Sponsor's protocol ID
- TN-401-0012
- Acronym
- RIDGE-1
- Status last verified
- Sep 2024
- First submitted
- 18 Jan 2024
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06228924
- Acronym / sponsor ID
- RIDGE-1 / TN-401-0012
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Tenaya TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 26 Mar 2024 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Oct 2029 (estimated)
- First posted
- 29 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Genetic: TN-401Dose for Cohort 1 will be 3E13 vg/kg |
| Cohort 2 | Experimental | Genetic: TN-401Dose for Cohort 2 will be 6E13 vg/kg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TN-401TN-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. | Genetic | Cohort 1, Cohort 2 |
Primary outcome
Number and severity of Adverse Events over the course of the study.
Time frame: 52 weeks
Number of Serious Adverse Events related to study drug.
Time frame: 5 years
3 secondary outcomes
To assess changes in daily PVC and NSVT counts
Time frame: Week 52
To assess frequency of ICD therapy administration
Time frame: Week 52
To assess frequency of sustained VT
Time frame: Week 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2025.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Niha Kamat contact
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TN-401 in people with Arrhythmogenic Right Ventricular Cardiomyopathy, run by Tenaya Therapeutics at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matthew Pollman, M.D. ((650) 416-1186, mpollman@tenayathera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and severity of Adverse Events over the course of the study. (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.