Arrhythmogenic Right Ventricular Cardiomyopathy
Conditions
Keywords
PKP2 Mutation Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Arrhythmogenic Cardiomyopathy (ACM), PKP2-associated ARVC, PKP2-ARVC, PKP2-ACM, Adeno Associated Virus (AAV), Adeno-Associated Virus Serotype 9 (AAV9), Gene Therapy, Gene Transfer, Genetic cardiomyopathy, Heart Failure
Brief summary
This is a multicenter, non-interventional study to observe the natural progression of the disease and to study the prevalence of pre-existing antibodies to AAV9 used for gene therapy in a population of patients with PKP2 gene-associated ARVC. Participation from all patients is encouraged regardless of interest in or eligibility for gene therapy.
Detailed description
Patients will receive standard of care treatments and assessments under the care of their healthcare provider. Biologic samples will be collected annually to measure cardiac and other related biomarkers. Clinical and observational data will be collected prospectively for up to 5 years from the date of enrollment, or until the patient withdraws consent/assent, undergoes heart transplantation, or dies. If consent is provided, there may be a one-time sample collection to evaluate genetics for research purposes. Quality of Life (QoL) questionnaires will be used to assess a patient's wellbeing and quality of life. If not included as part of a patient's standard of care, diagnostic Holter (or equivalent) monitoring will be required annually. No investigational product will be administered. Participation from all patients is encouraged regardless of interest in or eligibility for gene therapy.
Interventions
None listed
Sponsors
University of California, San Francisco
Brigham and Women's Hospital
New York University
University of Colorado, Denver
Johns Hopkins University
The Cleveland Clinic
Mayo Clinic
Medical University of South Carolina
Hopital Louis Pradel
Istituti Clinici Scientifici Maugeri SpA
The Queen Elizabeth Hospital
St George's University Hospitals NHS Foundation Trust
Royal Brompton & Harefield NHS Foundation Trust
Barts & The London NHS Trust
Skane University Hospital
Centro Cardiologico Monzino
Hôpital Haut-Lévêque
Nantes University Hospital
Pitié-Salpêtrière Hospital
Wuerzburg University Hospital
University Hospital Muenster
Tenaya Therapeutics
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
14 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ages 14-65 years, inclusive, at the time of consent * Pathogenic or likely pathogenic PKP2 gene mutation * Diagnosed with ARVC and meet 2010 Modified Task Force Criteria for ARVC as affected. * Functioning ICD
Exclusion criteria
* Currently receiving systemic immunosuppressive therapy, cytotoxic chemotherapy, immunoglobulin therapy or monoclonal antibody therapy * History of clinically significant liver disease, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tuberculosis infection * Previously dosed with any investigational or approved gene therapy product at any time * Concurrent participation in another interventional clinical trial unless approved by the Sponsor. Participation in a noninterventional study may be allowed at the investigator's discretion. * History of cardiac transplant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigate the seroprevalence of pre-existing antibodies to AAV9 in patients with PKP2-associated ARVC | 5 years |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the burden of illness in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To characterize arrhythmic risk in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To evaluate functional status and Quality of Life (QoL) in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To evaluate heart function as assessed by imaging in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
Other
| Measure | Time frame |
|---|---|
| • To monitor biomarkers associated with disease progression and inflammation in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To evaluate the effect of other cardiac mutations or other genetic variants that might affect the penetrance and/or expressivity of PKP2 mutations in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To evaluate health care utilization in patients with pathogenic or likely pathogenic PKP2 mutations | 5 years |
| To evaluate genetics associated with PKP2-associated ARVC | 5 years |
Countries
France, Germany, Italy, Sweden, United Kingdom, United States
Contacts
Primary ContactMatthew Pollman, MD
Backup ContactNiharika Kamat, MS
Outcome results
None listed