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) (RIDGE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Niharika Kamat, MS; Email: clinical.trials@tenayathera.com
• Study Contact Backup: Name: Matthew Pollman, MD; Phone Number: 650-209-8092; Email: mpollman@tenayathera.com

Study Locations

• France
  • Bron, France
    • Recruiting
    • Hôpital Louis Pradel
    • Contact: Philippe Chevalier, MD, PhD
  • Nantes, France, 44000
    • Recruiting
    • Nantes University Hospital
    • Contact: Vincent Probst, MD
  • Paris, France, 75013
    • Recruiting
    • Pitié-Salpêtrière Hospital
    • Contact: Estelle Gandjbakhch, MD, PhD
  • Pessac, France, 33604
    • Recruiting
    • Hopital Haut-Leveque
    • Contact: Frederic Sacher, MD, PhD
• Germany
  • Münster, Germany, 48149
    • Recruiting
    • University hospital Muenster
    • Contact: Eric Schulze-Bahr, MD
  • Würzburg, Germany, 97080
    • Recruiting
    • Wuerzburg University Hospital
    • Contact: Brenda Gerull, MD
• Italy
  • Milano, Italy, 20138
    • Recruiting
    • Centro Cardiologico Monzino
    • Contact: Claudio Tondo, MD
  • Pavia, Italy
    • Recruiting
    • Istituti Clinici Scientifici Maugeri SpA
    • Contact: Silvia Priori, MD, PhD
• Sweden
  • Malmö, Sweden, 214 28
    • Recruiting
    • Skåne University Hospital
    • Contact: Pyotr G Platonov, MD
• United Kingdom
  • Glasgow, United Kingdom, G514TF
    • Recruiting
    • The Queen Elizabeth Hospital
    • Contact: Caroline Coats, MD
  • London, United Kingdom, SW3 6NP
    • Recruiting
    • Royal Brompton & Harefield NHS Foundation Trust
    • Contact: Antonio Pantazis, MD
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • St. George's University Hospitals NHS Foundation Trust
    • Contact: Elijah Behr, MD
  • London, United Kingdom, E1 1BB
    • Recruiting
    • Barts & The London Health NHS Trust
    • Contact: Perry Elliott, MD
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Contact: Vasanth Vedantham, MD, PhD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado, Denver
      • Contact: Matthew Taylor, MD, PhD
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • John Hopkins University School of Medicine
      • Contact: Hugh G Calkins, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Neal Lakdawala, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: John Giudicessi, MD PhD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University
      • Contact: Larry Chinitz, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Wai Hong Wilson Tang, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Daniel Judge, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who are 14-65 years of age at the time of consent, and with confirmed mutations in PKP2 gene with a diagnosis of ARVC.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Retrospective and Prospective; Patients who meet the eligibility criteria are observed and data collected both prospectively and retrospectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Investigate the seroprevalence of pre-existing antibodies to AAV9 in patients with PKP2-associated ARVC	5 years

Secondary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 genetics associated with PKP2-associated ARVC	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): March 29, 2030
• Study Completion (Estimated): July 11, 2030

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Gene Therapy; Gene Transfer; Genetic cardiomyopathy; Adeno Associated Virus (AAV); PKP2 Mutation Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC); Arrhythmogenic Cardiomyopathy (ACM); PKP2-associated ARVC; PKP2-ARVC; PKP2-ACM; Adeno-Associated Virus Serotype 9 (AAV9)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Cardiomyopathies; Arrhythmogenic Right Ventricular Dysplasia
• Other Study ID Numbers: TN-401-0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No