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)

NCT06311708 | Recruiting

• 1 other identifier: TN-401-0011
• Study Type: observational
• Target: 200
• Locations: 6 countries
• Sites: 21

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.

Conditions

Arrhythmogenic Right Ventricular Cardiomyopathy

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

Outcome Measures

Primary Outcomes (1)

• Investigate the seroprevalence of pre-existing antibodies to AAV9 in patients with PKP2-associated ARVC

  5 years

Secondary Outcomes (4)

• 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 Outcomes (4)

• • 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

Study Arms (1)

Retrospective and Prospective

Patients who meet the eligibility criteria are observed and data collected both prospectively and retrospectively.

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (21)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Colorado, Denver

Aurora, Colorado, 80045, United States

RECRUITING

John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

New York University

New York, New York, 10016, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Hopital Louis Pradel

Bron, France

RECRUITING

Nantes University Hospital

Nantes, 44000, France

RECRUITING

Pitié-Salpêtrière Hospital

Paris, 75013, France

RECRUITING

Hôpital Haut-Lévêque

Pessac, 33604, France

RECRUITING

University Hospital Muenster

Münster, 48149, Germany

RECRUITING

Wuerzburg University Hospital

Würzburg, 97080, Germany

RECRUITING

Centro Cardiologico Monzino

Milan, 20138, Italy

RECRUITING

Istituti Clinici Scientifici Maugeri SpA

Pavia, Italy

RECRUITING

Skåne University Hospital

Malmo, 214 28, Sweden

RECRUITING

The Queen Elizabeth Hospital

Glasgow, G514TF, United Kingdom

RECRUITING

Barts & The London Health NHS Trust

London, E1 1BB, United Kingdom

RECRUITING

St. George's University Hospitals NHS Foundation Trust

London, SW17 0QT, United Kingdom

RECRUITING

Royal Brompton & Harefield NHS Foundation Trust

London, SW3 6NP, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be collected throughout the study 1 time each year to assess proteins and biomarkers associated with ARVC and to study existing antibodies to AAV9.

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Heart Failure

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiomyopathies; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Matthew Pollman, MD

CONTACT

650-209-8092; mpollman@tenayathera.com

Niharika Kamat, MS

CONTACT

clinical.trials@tenayathera.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 15, 2024
• Study Start: January 31, 2023
• Primary Completion (Estimated): March 29, 2030
• Study Completion (Estimated): July 11, 2030
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); FR (4); DE (2); IT (2); GB (4); SE (1)