Non-interventional Study of Seroprevalence of Pre-existing Antibodies Against Adenovirus-associated Virus Vector (AAV9) and the Progression of Disease in Patients With Plakophilin 2 (PKP2)-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Arrhythmogenic Right Ventricular Cardiomyopathy Clinical Trial

— RIDGE  

Official title:

Seroprevalence Study of Pre-existing Antibodies Against Adenovirus-associated Virus Vector (AAV9) in Patients With Plakophilin 2 (PKP2)-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06311708
• Other study ID #: TN-401-0011
• Status: Recruiting
• Start date: January 31, 2023
• Est. completion date: July 11, 2030

Study information

• Verified date: May 2024
• Source: Tenaya Therapeutics
• Contact: Matthew Pollman, MD
• Phone: 6504161186
• Email: mpollman[@]tenayathera.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 11, 2030
• Est. primary completion date: March 29, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arrhythmogenic Right Ventricular Cardiomyopathy
• Arrhythmogenic Right Ventricular Dysplasia
• Cardiomyopathies

Locations

Country	Name	City	State
France	Hopital Louis Pradel	Bron
France	Nantes University Hospital	Nantes
France	Pitié-Salpêtrière Hospital	Paris
France	Hôpital Haut-Lévêque	Pessac
Germany	Ludwig-Maximilians - University of Munich	München
Germany	University Hospital Muenster	Münster
Germany	Wuerzburg University Hospital	Würzburg
Italy	Centro Cardiologico Monzino	Milano
Italy	Istituti Clinici Scientifici Maugeri SpA	Pavia
Sweden	University Hospital, Linkoeping	Linköping
Sweden	Skåne University Hospital	Malmö
United Kingdom	The Queen Elizabeth Hospital	Glasgow
United Kingdom	Barts & The London Health NHS Trust	London
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	London
United Kingdom	St. George's University Hospitals NHS Foundation Trust	London
United States	University of Colorado, Denver	Aurora	Colorado
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	New York University	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California San Francisco	San Francisco	California

Sponsors (24)

Lead Sponsor

Collaborator

Tenaya Therapeutics

Barts & The London NHS Trust, Brigham and Women's Hospital, Centro Cardiologico Monzino, Hôpital Haut-Lévêque, Hopital Louis Pradel, Istituti Clinici Scientifici Maugeri SpA, Johns Hopkins University, Ludwig-Maximilians - University of Munich, Mayo Clinic, Medical University of South Carolina, Nantes University Hospital, New York University, Pitié-Salpêtrière Hospital, Royal Brompton & Harefield NHS Foundation Trust, Skane University Hospital, St George's University Hospitals NHS Foundation Trust, The Cleveland Clinic, The Queen Elizabeth Hospital, University Hospital Muenster, University Hospital, Linkoeping, University of California, San Francisco, University of Colorado, Denver, Wuerzburg University Hospital

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	• To monitor biomarkers associated with disease progression and inflammation in patients with pathogenic or likely pathogenic PKP2 mutations		5 years
Other	To evaluate genetics associated with PKP2-associated ARVC		5 years
Other	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
Other	To evaluate health care utilization in patients with pathogenic or likely pathogenic PKP2 mutations		5 years
Primary	Investigate the seroprevalence of pre-existing antibodies to AAV9 in patients with PKP2-associated ARVC		5 years
Secondary	To characterize the burden of illness in patients with pathogenic or likely pathogenic PKP2 mutations		5 years
Secondary	To characterize arrhythmic risk in patients with pathogenic or likely pathogenic PKP2 mutations		5 years
Secondary	To evaluate functional status and Quality of Life (QoL) in patients with pathogenic or likely pathogenic PKP2 mutations		5 years
Secondary	To evaluate heart function as assessed by imaging in patients with pathogenic or likely pathogenic PKP2 mutations		5 years