Danon Disease Natural History Study

Recruiting

• Conditions: Danon Disease
• Interventions: Other: No intervention

• Registration Number: NCT06214507
• Lead Sponsor: Rocket Pharmaceuticals Inc.

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.

Study Timeline

• Study First Submitted: 2023-11-17
• Study Start: 2023-12-20
• Study First Submitted QC: 2024-01-10
• Study First Posted: 2024-01-19
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2026-08-31
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Retrospective only	No intervention	-
Prospective	No intervention	-

Primary Outcome Measures

Name	Time	Method
Left Ventricular Mass Index (LVMI) by echocardiogram	12 and 24 months	Evaluation of change over duration of follow up

Secondary Outcome Measures

Name	Time	Method
CBC	12 and 24 months	CBC with differential
Serum Chemistry	12 and 24 months	Electrolytes
NYHA class	6, 12, 18 and 24 months	Evaluation of change over duration of follow up
KCCQ	6, 12, 18 and 24 months	Evaluation of change over duration of follow up
PedsQL	6, 12, 18 and 24 months	Evaluation of change over duration of follow up
Cardiac biomarkers (hsTnI)	12 and 24 months (when available)	Evaluation of change over duration of follow up
Cardiac biomarkers (NT-proBNP, BNP)	12 and 24 months (when available)	Evaluation of change over duration of follow up
ECG	6, 12, 18 and 24 months	Twelve-lead ECGs are relevant to describe changes in cardiac rhythm that may further contextualize the clinical events/endpointsevents/endpoints
Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization	12 and 24 months	Evaluation over duration of follow up
Six Minute Walk Test	6, 12,18 and 24 months	This test measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes.
Serum chemistry	12 and 24 months	LFT

Trial Locations

Locations (12)

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

University of Florida College of Medicine; 🇺🇸 Gainesville, Florida, United States

Washington University; 🇺🇸 St. Louis, Missouri, United States

Columbia University Medical Center/New York Presbyterian; 🇺🇸 New York, New York, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

German Heart Center Munich; 🇩🇪 München, Germany

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Azienda Ospedaliero Universitaria; 🇮🇹 Firenze, Italy

University College London - Great Ormond Street Institute of Child Health; 🇬🇧 London, United Kingdom