Clinical trial NCT06311708: 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)
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Tenaya Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of California, San Francisco
name: Brigham and Women's Hospital
name: New York University
name: University of Colorado, Denver
name: Johns Hopkins University
name: The Cleveland Clinic
name: Mayo Clinic
name: Medical University of South Carolina
name: Hopital Louis Pradel
name: Istituti Clinici Scientifici Maugeri SpA
name: The Queen Elizabeth Hospital
name: St George's University Hospitals NHS Foundation Trust
name: Royal Brompton & Harefield NHS Foundation Trust
name: Barts & The London NHS Trust
name: Skane University Hospital
name: Centro Cardiologico Monzino
name: Hôpital Haut-Lévêque
name: Nantes University Hospital
name: Pitié-Salpêtrière Hospital
name: Wuerzburg University Hospital
name: University Hospital Muenster
First posted: 2024-03-15
Enrollment: 200
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Investigate the seroprevalence of pre-existing antibodies to AAV9 in patients with PKP2-associated ARVC
timeFrame: 5 years
Secondary outcomes:
measure: To characterize the burden of illness in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
measure: To characterize arrhythmic risk in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
measure: To evaluate functional status and Quality of Life (QoL) in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
measure: To evaluate heart function as assessed by imaging in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
Other outcomes:
measure: • To monitor biomarkers associated with disease progression and inflammation in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
measure: To evaluate genetics associated with PKP2-associated ARVC
timeFrame: 5 years
measure: 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
timeFrame: 5 years
measure: To evaluate health care utilization in patients with pathogenic or likely pathogenic PKP2 mutations
timeFrame: 5 years
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: New York University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Bron
country: France
facility: Hopital Louis Pradel
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
city: Münster
country: Germany
facility: University Hospital Muenster
city: Würzburg
country: Germany
facility: Wuerzburg University Hospital
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Maugeri SpA
city: Malmö
country: Sweden
facility: Skåne University Hospital
city: Glasgow
country: United Kingdom
facility: The Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Barts & The London Health NHS Trust
city: London
country: United Kingdom
facility: St. George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust
Study officials:
References: