Overarching goal

“The overarching goal of this retrospective, multicenter, international study is to gain a better understanding of the Natural History of Danon disease, by collecting de-identified information from patients with this condition treated.” (opens the source at this quote in a new tab)
“This retrospective, multicenter, international, longitudinal, non- interventional study of DD patients with confirmed LAMP2 mutation aims at characterizing the Natural History of disease in males and females.” (opens the source at this quote in a new tab)

Primary objective

“Primary objective: Determine how specific cardiac manifestations in patients diagnosed with Danon disease change over time.” (opens the source at this quote in a new tab)
“Essential echocardiography and/or MRI-based parameters include: thickness of the Left Ventricular Posterior Wall at end-diastole (LVPWd); thickness of the Interventricular Septum at end-diastole (IVSd); Left Ventricular mass (LVmass); Left Ventricular Ejection Fraction (LVEF).” (opens the source at this quote in a new tab)

Secondary objectives

“Secondary objectives: Describe the progression of other cardiac and extracardiac manifestations in patients diagnosed with Danon disease, including, but not limited to: serologic markers of heart failure, serologic markers of muscle injury, risk and frequency of arrhythmias, comprehensive echocardiogram and MRI-based assessments of cardiomyopathy, overall survival, and event-free survival (as defined subsequently).” (opens the source at this quote in a new tab)

Exploratory objectives

“Exploratory objectives: Describe the diagnostic pathway of Danon disease, therapeutic management and local centers' approaches to genetic testing for LAMP2 mutations.” (opens the source at this quote in a new tab)
“Identify key Natural History trends to inform a prospective European Union (EU) natural history study and plan for a potential gene therapy trial for DD patients in the EU.” (opens the source at this quote in a new tab)

Support for the design of the RP-A501 pivotal trial

“The Real-world data collected from patients in this natural history study will help support the overall development and protocol design of the RP-A501 gene therapy pivotal trial to be submitted to the health authorities.” (opens the source at this quote in a new tab)

Identification of treating centers and planning of later studies

“Additionally, this study will allow identification of the core centers managing DD patients in several countries as well as the description of the disease characteristics, diagnosis pathway and disease progression.” (opens the source at this quote in a new tab)
“This will inform the development of patient profiles for future studies, including a potential prospective observational study to investigate the burden of disease among DD patients and an international patient registry for Danon disease.” (opens the source at this quote in a new tab)

Study identifiers, dates, and status

Item	Registry record
Sponsor protocol number	“RP-NI-A501-0122”
Sponsor	“Rocket Pharmaceuticals Inc.”
Recruitment status	“Completed”
Study start (actual)	“2022-09-26”
Primary completion (actual)	“2023-10-31”
Study completion (actual)	“2023-10-31”
First posted	“2022-09-22”
Last update posted	“2023-11-21”

Number of registered locations

“This study has 15 locations” (opens the source at this quote in a new tab)

Registered sites by country

Country	Site
Czechia	“Institut klinické a experimentální medicíny (IKEM)- Institute for Clinical and Experimental Medicine”
France	“CHU de Nantes, Hôpital Laennec”
France	“APHP, Hôpital de la Pitié Salppêtrière - Charles Foix”
France	“CHU de Rennes, Hôpital Pontchaïllou”
Ireland	“Mater Misericordiae University Hospital”
Italy	“Ospedale Papa Giovanni XXIII di Bergamo ASST Pap Giovanni XXIII Hospital”
Italy	“University of Florence Dept. of Experimental and Clinical Medicine”
Italy	“IRCCS Burlo Garogolo- Hospital Burlo Garofolo”
Spain	“Hospital Clínic de Barcelona - Barnaclínic+”
Spain	“Hospital Universitario de Bellvitge- Bellvitge University Hospital”
Spain	“Hospital Universitario La Paz - La Paz University Hospital”
Spain	“Hospital Universitario Puerta de Hierro Majadahonda Puerta de Hierro Majadahonda - University Hospital”
Spain	“Hospital Universitario Virgen de la Victoria- Virgen de la Victoria University Hosptial”
Spain	“Hospital Álvaro Cunqueiro”
Spain	“Hospital Universitario y Politécnico La Fe, Instituto De Investigación Sanitaria La Fe, La Fe University and Polytechnic Hospital”

Official title and registered design

“A Retrospective, Multicenter, International Study to Characterize the Natural History of Danon Disease” (opens the source at this quote in a new tab)
“This is a multicenter, international, non-interventional, natural history study designed to collect longitudinal retrospective clinical information on patients with Danon disease (DD).” (opens the source at this quote in a new tab)

Two study parts: feasibility assessment and retrospective chart review

“This study is composed of 2 parts:” (opens the source at this quote in a new tab)
“Feasibility study: to identify participating sites, assess site and team capabilities, confirm the site and investigator qualification for taking part in the study,” (opens the source at this quote in a new tab)
“Retrospective chart review: Data will be collected retrospectively by means of a chart review of living and/or deceased DD patients with a confirmed lysosome associated membrane protein-2 gene (LAMP2) mutation” (opens the source at this quote in a new tab)

Registered design details

Design element	Registry record
Study type	“Observational”
Observational model	“Cohort”
Time perspective	“Retrospective”
Sampling method	“Probability Sample”
Group 1	“Heart Transplant or Cardiac Assist Device”
Group 2	“No Intervention”
Plan to share individual participant data	“No”

Listing as a European retrospective data set within the external comparator: September 2023 company presentation

“EU Retrospective Natural History Study” (opens the source at this quote in a new tab)
“Prospective, Retrospective Natural History Study as External Comparator” (opens the source at this quote in a new tab)

Study population

“Female and male patients with confirmed diagnosis of Danon disease based on a genetic test positive for a mutation in LAMP2” (opens the source at this quote in a new tab)

Registered age and sex limits

Item	Registry record
Ages eligible for study	“6 Years and older”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

Inclusion criteria

Criterion	Quoted registry text
Age and sex	“Patients older than 6 years old and any sex.”
Genetic confirmation	“Patients with a confirmed genetic mutation in LAMP2.”
Living participants without heart transplantation or a cardiac assist device	“A minimum of 6 months of longitudinal data, including at least 2 echocardiograms or MRIs at least 6 months apart, prior to most recent follow-up visit or enrollment in Sponsor's gene therapy clinical trial.”
Deceased participants, or living participants with heart transplantation or a cardiac assist device	“At least 1 echocardiogram or MRI assessment prior to heart transplantation/ cardiac assist device placement or death”
Consent	“Informed consent/assent by the patient and/or their legally authorized representative (if the patient is living at the time of enrollment).”

Exclusion criterion

“Diagnosis of Danon disease without genetic testing confirmation.” (opens the source at this quote in a new tab)

Minimum follow-up data stated in the brief summary

“For living patients (who have not undergone heart transplantation or placement of a cardiac assist device), availability of at least 6-month cardiology follow-up data,” (opens the source at this quote in a new tab)
“For living patients who underwent heart transplantation or placement of a cardiac assist device, and for deceased patients, at least 1 MRI or echo assessment prior to heart transplantation/cardiac assist device placement or death.” (opens the source at this quote in a new tab)

No study intervention

“non-interventional” (opens the source at this quote in a new tab)

Standard-of-care procedures that define the registered groups

Registered item	Quoted registry text
“Procedure: Heart Transplant”	“Patients who have undergone a heart transplant as standard of care (SOC) procedure”
“Device: Cardiac Assistive Device”	“Patients who have undergone a placement of a cardiac assistive device”

Description of current treatment in the registry record

“There is currently no therapy available to cure, or even prevent disease progression.” (opens the source at this quote in a new tab)
“DD treatment is thus primarily supportive therapy, and survival beyond 25 years without a cardiac transplantation is improbable for afflicted male patients.” (opens the source at this quote in a new tab)

Primary outcome definitions

Outcome measure	Parameter as described	Time frame
“Cardiac Manifestations- LVPWd”	“thickness of the left ventricular posterior wall end diastole and end systole (LVPWd)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations- lVSd”	“thickness of the left ventricular systolic dysfunction (IVSd)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations- LVmass”	“left ventricular mass (LVmass)”	“Retrospective minimum of 6 months”
“Cardiac Manifestations - LVEF”	“left ventricular ejection fraction (LVEF)”	“Retrospective minimum of 6 months”

Analysis common to the four primary outcomes

“Descriptive analysis will be conducted to characterize specific cardiac manifestations in patients diagnosed with Danon disease, and changes over time.” (opens the source at this quote in a new tab)
“Data collected will be analyzed by 6-month intervals and by the changes from initial evaluation over each 6-month interval.” (opens the source at this quote in a new tab)

Parameter definitions in the detailed description

“Essential echocardiography and/or MRI-based parameters include: thickness of the Left Ventricular Posterior Wall at end-diastole (LVPWd); thickness of the Interventricular Septum at end-diastole (IVSd); Left Ventricular mass (LVmass); Left Ventricular Ejection Fraction (LVEF).” (opens the source at this quote in a new tab)

Stated relation between cardiac disease severity and prognosis

“Most men and many women with LAMP2 gene mutations will develop cardiac disease that includes hypertrophic cardiomyopathy and/or dilated cardiomyopathy, cardiac pre-excitation syndrome, and a propensity for arrhythmias.” (opens the source at this quote in a new tab)
“The prognosis is directly related to the severity of the cardiac disease, and many patients will die from sudden cardiac death.” (opens the source at this quote in a new tab)

Secondary outcomes: serologic markers

Outcome measure	Marker as described	Time frame
“Serologic Markers & Imaging - BNP”	“serologic markers of heart failure which include B-type natriuretic peptide (BNP)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging Pro-BNP”	“serologic markers of heart failure which include Pro- B-type natriuretic peptide (Pro-BNP)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- CK-MB”	“serologic markers of heart failure which include creatine kinase - MB (CK-MB)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- Troponin”	“serologic markers of heart failure which include Troponin”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- CPK”	“serologic markers of muscle injury, which include creatine phosphokinase (CPK)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- transaminases”	“serologic markers of muscle injury, which include transaminases”	“Retrospective minimum of 6 months”

Secondary outcomes: echocardiogram and magnetic resonance imaging assessments

Outcome measure	Assessment as described	Time frame
“Serologic Markers & Imaging- Echo/MRI”	“measures of cardiac hypertrophy or dilation”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- BP”	“measures of systolic and diastolic function”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- GLS”	“measures of Global Longitudinal Strain (GLS)”	“Retrospective minimum of 6 months”
“Serologic Markers & Imaging- E/A”	“measures of mitral inflow ratio of the early (E) to late (A) (ventricular filling velocities (E/A))”	“Retrospective minimum of 6 months”

Descriptive statistics planned for serologic and imaging outcomes

“Mean values, standard deviations, medians and changes in means will be provided” (opens the source at this quote in a new tab)

Secondary outcomes: arrhythmia, device placement, and survival

Outcome measure	Measure description	Time frame
“Arrhythmias”	“Time to event (risk of arrhythmia), for each of the following: supraventricular arrhythmias and non-sustained ventricular arrhythmias on Holter or similar monitoring, treatment with anti-arrhythmic medications”	“Retrospective minimum of 6 months”
“Wolf-Parkinson-White syndrome”	“Time to event of Wolf-Parkinson-White syndrome (WPW) on electrocardiogram”	“Retrospective minimum of 6 months”
“ICD Placement”	“Time to event of Implantable cardioverter-defibrillators (ICD) placement”	“Retrospective minimum of 6 months”
“Reason for ICD Placement”	“Reasoning for ICD placement will be summarized by frequency of the reasons”	“Retrospective minimum of 6 months”
“Overall Survival”	“Overall survival will be analyzed using Kaplan-Meier estimates.”	“Retrospective minimum of 6 months”
“Event-free survival”	“Event-free survival (EFS) will be analyzed using Kaplan-Meier estimates.”	“Retrospective minimum of 6 months”

Event-free survival by event tier

“EFS will be provided for Tier 1 events, Tier 1 + Tier 2 events, and Tier 1 + Tier 2 +Tier 3 events.” (opens the source at this quote in a new tab)

Definition of the event tiers

No evidence found.

Planned enrollment

No evidence found.

Actual enrollment: registry record

Enrollment type	Participants
Actual	“59”

Enrollment status of the European retrospective study in September 2023

“Enrollment complete; analysis in Q4 2023” (opens the source at this quote in a new tab)

Analyzed population

No evidence found.

Registered groups

Group	Quoted registry text
“Heart Transplant or Cardiac Assist Device”	“For living patients who underwent heart transplantation or placement of a cardiac assist device, and for deceased patients, at least 1 MRI or echo assessment prior to heart transplantation/cardiac assist device placement or death.”
“No Intervention”	“for living patients (who have not undergone heart transplantation or placement of a cardiac assist device), availability of at least 6-month cardiology follow-up data”

Analysis intervals

“Data collected will be analyzed by 6-month intervals and by the changes from initial evaluation over each 6-month interval.” (opens the source at this quote in a new tab)

Censoring in survival analyses

“Patients lost to follow-up or who complete the study will be censored at the last follow-up time.” (opens the source at this quote in a new tab)

Sex of participants in the European retrospective study: September 2023 company presentation

Data set	Males	Females
“EU Retrospective Natural History Study”	“21 Males”	“38 Females”

Other baseline characteristics

No evidence found.

Study results

No evidence found.

Planned timing of the analysis as stated in September 2023

“Enrollment complete; analysis in Q4 2023” (opens the source at this quote in a new tab)

Source of the natural history figures in the September 2023 company presentation

“Reflects estimated LV Mass increase over 12-18M for DD patients based on retrospective natural history data-set (shown on slide 20).” (opens the source at this quote in a new tab)
“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)

Source of the natural history comparison in the October 2026 company presentation

“Differs significantly from expanded natural history data” (opens the source at this quote in a new tab)
“Unpublished data from International Danon Disease Registry” (opens the source at this quote in a new tab)

Summary

RP-NI-A501-0122 is a retrospective chart review with no study intervention, sponsored by Rocket Pharmaceuticals, the developer of RP-A501. The registry record reports 59 participants enrolled at 15 sites in 5 European countries and completion on 2023-10-31. No results are posted on the record and no results publication was identified; the September 2023 company presentation lists an “EU Retrospective Natural History Study” of 21 male and 38 female participants (59 in total) with “analysis in Q4 2023”. Data were collected by chart review from echocardiograms or magnetic resonance imaging already performed, and the record sets no imaging method or schedule; a living participant without heart transplantation or a cardiac assist device needed at least 2 imaging assessments at least 6 months apart, and a deceased participant or a participant with transplantation or a device needed at least 1 assessment. The study enrolled participants of either sex older than 6 years, including deceased participants and participants with heart transplantation or a cardiac assist device, whereas the pivotal trial of RP-A501 enrolls males aged 8 years and older with a left ventricular ejection fraction of at least 50% and excludes prior transplantation. The primary outcomes are left ventricular posterior wall thickness, interventricular septal thickness, left ventricular mass, and ejection fraction; the record does not list left ventricular mass index, the measure used in the pivotal trial's primary endpoint. The outcome descriptions for posterior wall and septal thickness on the record differ from the definitions in its detailed description, and the event tiers used for event-free survival are not defined. The record states that the data support the protocol design of the pivotal trial, and the September 2023 presentation lists the study among three natural history data sets under the heading “Prospective, Retrospective Natural History Study as External Comparator”; how its participants enter the comparison has not been published. The natural history figures in the September 2023 and October 2026 company presentations are attributed to “Unpublished data from International Danon Disease Registry”.