Clinical trial NCT06214507: Danon Disease Natural History Study
Official title: An Observational Study of Genetic Cardiomyopathy, Danon Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Danon Disease
Keywords: Danon Disease
LAMP2
Lysosome-associated membrane protein 2
Cardiomyopathy
X-linked
Lead sponsor: Rocket Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-19
Enrollment: 46
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male patients 8 years of age and over, Female patients 30 years of age and under (at the point of enrollment) with confirmed Danon disease recruited from a range of applicable care settings.

Brief summary: The goal of this international observational study is to learn about the natural history of Danon disease in male patients \>8 years of age and female patients \<30 years of age. The key objectives include assessing change over time in cardiac structure (left ventricular mass and wall thickness), cardiac biomarkers, symptoms, and quality of life and the incidence of clinical events such as HF hospitalization, cardiac transplantation, and death.

Detailed description: This is an international observational study with both retrospective and prospective data collection. The study is designed to describe the natural history of Danon disease which is a rare x-linked genetic disorder and one of the most severe and penetrant forms of inherited cardiomyopathy. This study will collect data about the clinical course of Danon disease including signs and symptoms, key clinical events, and the impact of the disease on quality of life managed with current standard of care. A hybrid (retrospective and prospective data collection) approach is being taken with the aim of achieving robust and longitudinal data generation.

Subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.

Eligibility criteria: Inclusion Criteria:

Prospective Cohort:

1. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory
2. Patient or parent/legal guardian are capable and willing to provide signed informed consent
3. Age ≥ 8 years at enrollment

   Female Prospective Cohort:
4. Evidence of left ventricular hypertrophy with preserved systolic function in the 12 months prior to or at enrollment as defined by each of the following:

   Retrospective (only) Cohort:
5. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory
6. Patient or parent/legal guardian are capable and willing to provide signed informed consent, as required by local regulations
7. Age ≥ 8 years at enrollment
8. Prior cardiac transplantation or prior mechanical circulatory support
9. At least 30 days of retrospective medical records available prior to cardiac transplantation or mechanical circulatory support

   Female Retrospective (only) Cohort:
10. Prior evidence of left ventricular hypertrophy.

Exclusion Criteria:

All Cohorts:

1. Concurrent enrollment in any other clinical investigation involving use of an investigational agent for any condition at time of enrollment to this study that could confound interpretation of this study
2. Previous treatment with a gene therapy

   Prospective Cohort:
3. Prior mechanical circulatory support at time of enrollment to this study
4. Prior cardiac transplantation at time of enrollment to this study

   Female patients:
5. Age \>30 years at enrollment

Primary outcomes:
measure: Left Ventricular Mass Index (LVMI) by echocardiogram
timeFrame: 12 and 24 months
Secondary outcomes:
measure: Cardiac biomarkers (hsTnI)
timeFrame: 12 and 24 months (when available)
measure: Cardiac biomarkers (NT-proBNP, BNP)
timeFrame: 12 and 24 months (when available)
measure: NYHA class
timeFrame: 6, 12, 18 and 24 months
measure: KCCQ
timeFrame: 6, 12, 18 and 24 months
measure: PedsQL
timeFrame: 6, 12, 18 and 24 months
measure: Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization
timeFrame: 12 and 24 months
measure: Six Minute Walk Test
timeFrame: 6, 12,18 and 24 months
measure: CBC
timeFrame: 12 and 24 months
measure: Serum Chemistry
timeFrame: 12 and 24 months
measure: ECG
timeFrame: 6, 12, 18 and 24 months
measure: Serum chemistry
timeFrame: 12 and 24 months
measure: Serum chemistry
timeFrame: 12 and 24 months
measure: Serum chemistry
timeFrame: 12 and 24 months
measure: Serum chemistry
timeFrame: 12 and 24 months
measure: Serum chemistry
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: München
country: Germany
facility: German Heart Center Munich
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria
city: London
country: United Kingdom
facility: University College London - Great Ormond Street Institute of Child Health
Study officials:
References: