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.
TN-401 is an investigational gene therapy designed to replace the mutated gene with a working PKP2 gene to address the underlying causes of ARVC.
- TN-401 uses an adeno-associated virus (AAV) as a vehicle (called a vector) 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
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:
- How safe TN-401 is for 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 how 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. To be eligible for this trial, a person must:
To be eligible for this clinical trial, a person must:
- Be 18 to 65 years old
- Have ARVC caused by mutations in the PKP2 gene
- Have a working transvenous implantable cardiac defibrillator (ICD) with remote monitoring
- Have frequent daily arrhythmias such as premature ventricular contractions (PVCs)
- Have a low level of antibodies to AAVs
These are not all of the eligibility criteria for this clinical trial.
If a person is not eligible for RIDGE-1 clinical trial, 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.
- You can also visit ClinicalTrials.gov and enter identifier number NCT06228924.
- Or share this RIDGE-1 Clinical Trial Fact Sheet with your doctor.
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 time1,2
- After the first treatment with AAV gene therapy, a person’s immune system makes antibodies to the AAV vector. 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 the incorrect cell. If this happens, healthy cells may be damaged and cause other illnesses.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 cells.5
- 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
(Up to 8 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
- How to leave 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 why 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 16 follow up visits after leaving the hospital to monitor safety and changes in heart function and ARVC symptoms
About 4 years
Long-term follow-up
(5 visits total, 1 per year) 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 around the world
- Visit the RIDGE-1 clinical trial page on ClinicalTrials.gov (NCT06228924) for more information about the clinical trial and which centers are participating
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 March 30, 2023. 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. National Institutes of Health, National Cancer Institute. NCI dictionary of cancer terms. Accessed July 20, 2023. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cardiac-catheterization.