ARVC Studies

Our StudiesRIDGE-1

RIDGE™-1:

A Clinical Trial for People with PKP2-associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

The RIDGE™-1 clinical trial will assess a gene therapy called TN-401 for the potential treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations (changes) in the PKP2 gene.

Click here to learn more about how mutations in the PKP2 gene cause ARVC.

TN-401 is an investigational gene therapy designed to address the underlying genetic cause of ARVC.

  • TN-401 uses the adeno-associated virus 9 (AAV9) capsid as a vehicle designed to deliver a working PKP2 gene to the muscle cells in the heart
  • Once in these cells, the working gene delivered by TN-401 may help make the protein needed to restore typical heart function
  • TN-401 is given as a one-time intravenous (IV) infusion
Click here to learn more about TN-401 gene therapy.

What is the purpose of the RIDGE-1 clinical trial?

RIDGE-1 is a Phase 1b clinical trial. This means it is the first trial to study TN-401 in humans. The goals are to understand:

  • The safety of TN-401 in humans
  • Any potential side effects
  • The best dose of TN-401
  • The effects of TN-401 on the human body

The RIDGE-1 clinical trial will also look at the way TN-401 affects overall health and quality of life based on feedback from participants and their doctors.

AAV gene therapy does carry some risk. Read about known risks of AAV gene therapy here, or ask your doctor for more information.

In collaboration with experts in ARVC and gene therapy, Tenaya carefully developed the plans for the RIDGE-1 clinical trial with the advice of the FDA. These plans are called the protocol. The protocol for the RIDGE-1 clinical trial is similar to protocols used in other gene therapy clinical trials around the world.

Who can take part in the RIDGE-1 clinical trial?

The RIDGE-1 clinical trial will enroll a limited number of people in the United States and the United Kingdom. 

You may be able to take part in the trial if you:

  • Have ARVC caused by mutations in the PKP2 gene
  • Are 18 to 65 years old
  • If you have not yet had a VT ablation or have had an ablation at least six months ago
  • Have a working implantable cardiac defibrillator (ICD) with remote monitoring
  • Have frequent daily arrhythmias such as premature ventricular contractions (PVCs)
  • Have a low level of antibodies to the AAVs

These are not all of the eligibility criteria. Clinical trial staff will evaluate interested people and determine if they are eligible to take part in RIDGE-1.

If a person is not eligible for RIDGE-1, there may be opportunities to take part in future Tenaya studies for people with genetic ARVC that may have different eligibility criteria.

Click here for more information about antibody testing and an ongoing study to learn more about AAV antibodies in people with ARVC.

Participation in the RIDGE-1 clinical trial is entirely voluntary. There is no cost to participate in this clinical trial. Participants can choose whether they want to take part in the study, and participants can change their mind at any time.

For more information about the RIDGE-1 clinical trial, talk to your doctor, contact clinical.trials@tenayathera.com or patient.advocacy@tenayathera.com.

What are the risks associated with AAV gene therapy?

Clinical trials of AAV gene therapies are still ongoing and not all of the risks are known. Known risks today include:

  • The immune system may recognize the gene therapy as a harmful intruder. AAVs do not cause diseases in people. However, the immune system is designed to remove anything it does not recognize as part of a person’s body. The immune system may react by attacking the treatment before it has a chance to work.1,2
    • Some studies of AAV and other forms of gene therapy show that immune system reactions may affect a person’s liver2
    • Medicines that suppress or subdue the immune system are typically given before a person receives AAV gene therapy to help prevent or reduce this reaction3
  • Currently, a person can receive AAV gene therapy only once; it cannot be re-dosed or administered in a larger dose at a later time.1,2
    • After the first treatment with AAV gene therapy, a person’s immune system makes antibodies to the AAV capsid. If the body sees the same AAV again, it will attack it before it has a chance to work4
  • AAV gene therapy may deliver a working gene to cell or tissue types that are not their intended target. This may cause illness or harm other cells.1,4
    • This is why the working gene is packaged with specific instructions which tell the gene what to do in target cells and reduces potential effects on other cells5
  • Participation in an AAV gene therapy clinical trial may prevent an individual from participating in clinical trials for other AAV gene therapies in the future. Although many clinical trials of AAV gene therapies have been completed to date, ask your healthcare provider about the known risks of AAV gene therapy.

What to expect in the RIDGE-1 clinical trial

(8-12 weeks)

Screening

to determine whether a person can participate

Informed Consent

to ensure a person understands:

  • The purpose of the clinical trial
  • All participants will receive TN-401, the investigational gene therapy
  • Expectations for participation including required visits, procedures, and tests
  • Potential risks and benefits
  • Options for leaving the clinical trial if desired

Pre-dose Activites

  • The clinical trial doctor will start the participant on medicines that will reduce the chances that your immune system will block the effect of TN-401
  • The doctor will review the reason these medicines are needed, the amount of time the participant will need to take these medicines, and any potential side effects
  • The doctor will gather more information about the participant’s health with a physical exam, blood test, echocardiogram, and by taking a small sample of heart muscle during a biopsy, in which a flexible tube (catheter) is inserted into a large vein in the neck and guided into the heart6

Infusion of TN-401

  • The infusion of TN-401 typically takes 2 to 4 hours
  • Hospitalization for 8 days for close monitoring, management, and treatment of any possible side effects

First-year follow-up visits

approximately 19 follow up visits after leaving the hospital to monitor safety and changes in heart function and ARVC symptoms

Most visits will be in person at the trial site with a select number of visits completed by phone or via home visits.

About 4 years

Long-term follow-up

(5 visits total, roughly 6 months after the 1st year and then 1 visit per year up to Year 5) to monitor safety and changes in heart function and ARVC symptoms over time

Participants can choose whether they want to take part in the clinical trial, and they can change their mind at any time.

Clinical trial locations

  • Tenaya is working with leading experts in gene therapy and ARVC to open clinical trial sites in the US and UK. 
  • Visit the RIDGE-1 clinical trial page on ClinicalTrials.gov (NCT06228924) for more information about the clinical trial.
  • Use the map below to search for participating centers.

United States Locations

California Locations

San Francisco, California, United States, 94143

Recruiting

University of California San Francisco

Contact: Vasanth Vedantham, MD

Colorado Locations

Aurora, Colorado, United States, 80045

Recruiting

University of Colorado - Anschutz Medical Campus

Contact: Matthew Taylor, MD

Maryland Locations

Baltimore, Maryland, United States, 21287

Recruiting

Johns Hopkins University

Contact: Andreas Barth, MD

Massachusetts Locations

Boston, Massachusetts, United States, 02115

Recruiting

Brigham and Women's Hospital

Contact: Neal Lakdawala, MD

Minnesota Locations

Rochester, Minnesota, United States, 55905

Recruiting

Mayo Clinic

Contact: John R. Giudicessi, MD

New York Locations

New York, New York, United States, 10016

Recruiting

NYU Langone Health

Contact: Larry Chinitz, MD

Ohio Locations

Cleveland, Ohio, United States, 44195

Not yet recruiting

Cleveland Clinic

Contact: Milind Desai, MD

Scroll to see more locations

If you are interested in participating:

Talk to your doctor about whether you may be a candidate for this clinical trial

Visit ClinicalTrials.gov (NCT06228924) to learn more, including where the clinical trial is being conducted. Check back often as the list will be updated when new clinical trial sites are available

Contact clinical.trials@tenayathera.com or patient.advocacy@tenayathera.com to request more information

THE USE OF TN-401 DESCRIBED HERE IS INVESTIGATIONAL. SAFETY AND EFFICACY HAVE NOT BEEN ESTABLISHED. TN-401 HAS NOT BEEN APPROVED BY THE U.S. FOOD AND DRUG ADMINISTRATION OR ANY OTHER COUNTRY’S HEALTH AUTHORITY OR REGULATORY AGENCY.

Expand for References

1. Au HKE, et al. Gene therapy advances: a meta-analysis of AAV usage in clinical settings. Front Med. 2022;8:809118. https://doi.org/10.3389/fmed.2021.809118. 2. Delire B, et al. Immunotherapy and gene therapy: new challenges in the diagnosis and management of drug-induced liver injury. Front Pharmacol. 2022;12:786174. https://doi.org/10.3389/fphar.2021.786174. 3. Xiang Z, et al. The effect of rapamycin and ibrutinib on antibody responses to adeno-associated virus vector mediated gene transfer. Hum Gene Ther. 2022;33:614-624. https://doi.org/10.1089/hum.2021.258. 4. Gene Therapy. Mayo Foundation for Medical Education and Research; 2022. https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619. Accessed April 15, 2024. 5. Domenger C, Grimm D. Next-generation AAV vectors – do not judge a virus (only) by its cover. Human Molecular Genetics. 2019;28:R3-R14. https://doi.org/10.1093/hmg/ddz148. 6. Cardiac catheterization. National Institutes of Health, National Cancer Institute. NCI dictionary of cancer terms. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cardiac-catheterization. Accessed April 15, 2024.