Registered study goal

“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 (8 to 50 years of age).” (opens the source at this quote in a new tab)
“The study is designed to describe the natural history of Danon disease, a rare X-linked genetic disorder, and one of the most severe and penetrant forms of inherited cardiomyopathy.” (opens the source at this quote in a new tab)

Data to be collected on the clinical course under standard care

“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 as managed with the current standard of care.” (opens the source at this quote in a new tab)

External control arm for RP-A501 trial participants

“A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.” (opens the source at this quote in a new tab)

“The cohort of patients in the study will provide data about Danon disease managed with available standard of care and thus, serve as an external comparator arm for the Phase 2 trial and provide important context to assess the efficacy of RP-A501 in patients enrolled in the Phase 2 trial.” (opens the source at this quote in a new tab)

Stated need for prospective collection at pre-specified intervals

“Given the rarity of the condition, most prior efforts characterizing disease progression have utilized retrospective records that include variable diagnostics/testing intervals.” (opens the source at this quote in a new tab)
“To describe the Natural History (NH) of DD in a comprehensive/unbiased way, there is a need to standardize a protocol for prospectively collecting cardiac testing at pre-specified intervals, while taking advantage of retrospectively collected patient data.” (opens the source at this quote in a new tab)

Study identifiers, dates, and status

Item	Registry record
Sponsor protocol number	“RP-NI-A501-0223”
Other sponsor identifier	“LAMPLIGHT-NH”
Sponsor	“Rocket Pharmaceuticals Inc.”
Recruitment status	“Recruiting”
Study start (actual)	“2023-12-20”
Primary completion (estimated)	“2029-12”
Study completion (estimated)	“2030-03”
First posted	“2024-01-19”
Last update posted	“2026-07-28”

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
United States	“Phoenix Children's Hospital”
United States	“University of California, San Diego”
United States	“Children's Hospital Colorado”
United States	“University of Florida College of Medicine”
United States	“University of Michigan”
United States	“Washington University”
United States	“Columbia University Medical Center/New York Presbyterian”
United States	“University of Texas, Southwestern”
United States	“Texas Children's Hospital”
Germany	“German Heart Center Munich”
Israel	“Sheba Medical Center”
Italy	“Azienda Ospedaliera Universitaria Meyer IRCCS”
Spain	“Sant Joan de Déu Hospital”
Spain	“Hospital Universitario Puerta de Hierro Majadahonda”
United Kingdom	“University College London - Great Ormond Street Institute of Child Health”

United Kingdom ethics review and study duration

Item	Research summary
Integrated Research Application System identifier	“339721”
Sponsor organisation	“Rocket Pharmaceuticals, Inc.”
Duration of study in the United Kingdom	“2 years, 4 months, 17 days”
Research ethics committee	“South Central - Berkshire Research Ethics Committee”
Research ethics committee reference	“24/SC/0094”
Date of opinion	“6 Jun 2024”
Opinion	“Further Information Favourable Opinion”

Official title and hybrid data collection

“An Observational Study of Genetic Cardiomyopathy, Danon Disease” (opens the source at this quote in a new tab)
“This is an international observational study with both retrospective and prospective data collection.” (opens the source at this quote in a new tab)
“A hybrid (retrospective and prospective data collection) approach is being used to generate robust and longitudinal data.” (opens the source at this quote in a new tab)

“The current study is a multi-country, observational, non-interventional, longitudinal study with prospective and retrospective data collection that aims to describe the natural course of Danon disease progression.” (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	“Prospective”
Sampling method	“Non-Probability Sample”
Group 1	“Prospective Cohort”
Group 2	“Retrospective Cohort”
Intervention	“Other: No intervention”

Visit schedule and duration of prospective follow-up

“Yearly lab and echocardiogram (ECHO) and electrocardiogram (EKG) assessments, reporting on key events, and the impact of the disease on quality of life, as it is managed with current treatments, for a total of 3 years.” (opens the source at this quote in a new tab)
“Visits take place at a study site or, in some cases, can be conducted remotely.” (opens the source at this quote in a new tab)

Regulatory basis for a natural history comparator: December 2022 statement

“we anticipate utilizing a single arm open-label trial design with a robust natural history comparator, pursuant to the FDA’s acknowledgment of the challenges associated with executing a randomized controlled trial in Danon Disease” (opens the source at this quote in a new tab)
“We look forward to continued dialogue with the FDA on the design for our proposed pivotal trial, including discussion of appropriate external controls for the study and appropriate endpoints to support accelerated approval.” (opens the source at this quote in a new tab)

Natural history comparator in the pivotal trial design aligned with the FDA: September 2023 statements

“Final alignment reached on a single arm, open-label study with natural history comparator and a biomarker based co-primary endpoint consisting of LAMP2 protein expression and Left Ventricular (LV) Mass” (opens the source at this quote in a new tab)
“A global natural history study will serve as an external comparator and run concurrently to the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

“NHS to serve as external comparator” (opens the source at this quote in a new tab)
“Pivotal, global, single-arm, open label study with external comparator” (opens the source at this quote in a new tab)

Natural history data sets named as the external comparator in September 2023

“Prospective, Retrospective Natural History Study as External Comparator” (opens the source at this quote in a new tab)
“Allows for robust comparisons and aligned with FDA guidance” (opens the source at this quote in a new tab)

Data set	Males	Females	Status
“Prospective Natural History Study”	“9 Males”	“1 Female”	“Initiated in 2019, study complete”
“US Retrospective Natural History”	“51 Males”	“67 Females”	“Initiated in 2006”
“EU Retrospective Natural History Study”	“21 Males”	“38 Females”	“Enrollment complete; analysis in Q4 2023”

Planned sponsor-initiated prospective study and its design elements: September 2023

“To be expanded through an additional prospective Rocket-initiated natural history study” (opens the source at this quote in a new tab)
“Entry criteria and endpoints similar to Phase 2 trial” (opens the source at this quote in a new tab)
“Appropriate matching to ensure robust comparisons” (opens the source at this quote in a new tab)
“Retrospective data collection to supplement prospective evaluation to ensure sufficient comparative data” (opens the source at this quote in a new tab)

Use of the external comparator arm at each time point: September 2023

“Each patient’s baseline AND matched external comparator arm together provide robust control data to assess treatment effect” (opens the source at this quote in a new tab)
“External comparator arm serves as control at each timepoint” (opens the source at this quote in a new tab)
“Note: Illustrative representation of potential treatment effects versus natural history” (opens the source at this quote in a new tab)

External comparator role: Form 10-K filed February 2026

“A global natural history study is also running concurrently to the Phase 2 pivotal trial and will serve as an external comparator.” (opens the source at this quote in a new tab)

Description of the natural history study: Form 10-Q filed August 2026

“A global natural history study is also running concurrently with the Phase 2 pivotal trial.” (opens the source at this quote in a new tab)

Referral of male participants from the natural history study to the gene therapy study

“If a male patient joins the Natural History study and is interested in learning more about participation in the Gene Therapy study, a discussion should be had with the Natural History study Principal Investigator to receive a referral to the Gene Therapy study team.” (opens the source at this quote in a new tab)

Study population

“Male patients 8 years of age and over, Female patients 8 to 50 years of age (at the point of enrollment) with confirmed Danon disease recruited from a range of applicable care settings.” (opens the source at this quote in a new tab)

Registered age and sex limits

Item	Registry record
Ages eligible for study	“8 Years and older”
Sexes eligible for study	“All”
Accepts healthy volunteers	“No”

Inclusion criteria: prospective cohort

Criterion	Quoted registry text
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory”
Consent	“Patient or parent/legal guardian are capable and willing to provide signed informed consent”
Age	“Age ≥ 8 years at enrollment”
Additional criterion for females	“Evidence of left ventricular hypertrophy in the 12 months prior to or at enrollment.”

Inclusion criteria: retrospective-only cohort

Criterion	Quoted registry text
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene by a CLIA-certified genetic testing laboratory”
Consent	“Patient or parent/legal guardian are capable and willing to provide signed informed consent, as required by local regulations”
Age	“Age ≥ 8 years at enrollment”
Prior advanced heart failure therapy	“Prior cardiac transplantation or prior mechanical circulatory support”
Available records	“At least 30 days of retrospective medical records available prior to cardiac transplantation or mechanical circulatory support”
Additional criterion for females	“Prior evidence of left ventricular hypertrophy.”

Exclusion criteria

Cohort	Quoted registry text
All cohorts	“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”
All cohorts	“Previous treatment with a gene therapy”
Prospective cohort	“Prior mechanical circulatory support at time of enrollment to this study”
Prospective cohort	“Prior cardiac transplantation at time of enrollment to this study”
Prospective cohort	“Female patients: Age >51 years at enrollment”

Eligibility as described on the recruitment website

“Males, age 8 years or older” (opens the source at this quote in a new tab)
“Females, age 8 to 50 years” (opens the source at this quote in a new tab)
“Diagnosed with Danon disease” (opens the source at this quote in a new tab)

Key eligibility criteria of the pivotal trial that the external control arm supports

Criterion	Quoted registry text
Sexes eligible for study	“Male”
Age	“Age ≥8 years.”
Genetic confirmation	“Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.”
Systolic function	“Left ventricular ejection fraction (LVEF) ≥ 50%.”
Functional class	“New York Heart Association (NYHA) Class II to III.”
Troponin	“High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (ULN) ≤ 12 months prior to screening.”
Excluded: prior transplantation	“Prior cardiac or other organ (lung, liver, other) transplantation.”

No study intervention

“Other: No intervention” (opens the source at this quote in a new tab)

“You do not receive any new therapy as part of the study.” (opens the source at this quote in a new tab)

Continuation of standard care during the study

“People in the study stay on the treatments they already use and will continue to see their doctor for regular care.” (opens the source at this quote in a new tab)

“as managed with the current standard of care” (opens the source at this quote in a new tab)

Primary outcome definition

Outcome measure	Measure description	Time frame
“Left Ventricular Mass Index (LVMI) by echocardiogram”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”

Secondary outcomes: biomarkers, symptoms, quality of life, and clinical events

Outcome measure	Measure description	Time frame
“Cardiac biomarkers (hsTnI)”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36 (when available)”
“Cardiac biomarkers (NT-proBNP, BNP)”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36 (when available)”
“NYHA class”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“KCCQ-12”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“PedsQL”	“Evaluation of change over duration of follow up”	“Month 12, 24, 36”
“Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization”	“Evaluation over duration of follow up”	“Month 12, 24, 36”
“Six Minute Walk Test”	“This test measures the distance that a subject can quickly walk on a flat, hard surface in a period of 6 minutes.”	“Month 12, 24, 36”

Secondary outcomes: electrocardiogram, anti-AAV9 antibody titer, and laboratory tests at enrollment

Outcome measure	Measure description	Time frame
“ECG”	“Twelve-lead ECGs are relevant to describe changes in cardiac rhythm that may further contextualize the clinical events/endpoints”	“Month 12, 24, 36”
“Anti-AAV9 titer”	“Change in antibody assay findings over time”	“Month 12, 24, 36”
“CBC”	“CBC with differential”	“At enrollment”
“Serum Chemistry”	“Electrolytes”	“At enrollment”
“Serum chemistry”	“Creatinine”	“At enrollment”
“Serum chemistry”	“LDH”	“At enrollment”
“Serum chemistry”	“BUN”	“At enrollment”
“Serum chemistry”	“eGFR”	“At enrollment”
“Serum chemistry”	“LFT”	“At enrollment”

Primary endpoint of the pivotal trial that the external control arm supports

“Myocardial tissue expression of LAMP2 protein improved from baseline to ≥ Grade 1 (by IHC), AND, ≥ 10% decrease in LVMI from baseline.” (opens the source at this quote in a new tab)
“12 months post-infusion” (opens the source at this quote in a new tab)

Alignment of natural history endpoints with the pivotal trial: September 2023 statement

“Entry criteria and endpoints similar to Phase 2 trial” (opens the source at this quote in a new tab)

Company rationale for left ventricular mass as a measure of disease progression: September 2023

“Left ventricular hypertrophy is the most consistent phenotypic feature of disease progression” (opens the source at this quote in a new tab)
“Retrospective natural history shows year-over-year increases in LV mass in Danon disease patients” (opens the source at this quote in a new tab)
“Data from the Natural History Studies demonstrated increases in key echo parameters in DD that are known to predict disease progression in other types of cardiomyopathy” (opens the source at this quote in a new tab)

Interpretation of the pivotal trial primary endpoint in the context of the concurrent natural history study

“Primary endpoint will be assessed in the context of biomarkers, symptoms, QOL, clinical events derived from secondary endpoints and concurrent natural history study” (opens the source at this quote in a new tab)

Planned enrollment: registry record

Enrollment type	Participants
Estimated	“60”

Enrollment as of August 2026

“In parallel with the pivotal Phase 2 trial, Rocket’s global natural history study has enrolled more than 50 patients, including both males and females, building an increasingly robust longitudinal dataset to further characterize Danon disease.” (opens the source at this quote in a new tab)

Number of participants in the external control arm subset

No evidence found.

Analyzed population

No evidence found.

Registered cohorts

“Prospective Cohort” (opens the source at this quote in a new tab)
“Retrospective Cohort” (opens the source at this quote in a new tab)

Subset used as the external control arm

“A subset of patients will be used as an External Control Arm for comparison to RP-A501 Trial participants.” (opens the source at this quote in a new tab)

Matching of the external comparator arm: September 2023 statements

“Appropriate matching to ensure robust comparisons” (opens the source at this quote in a new tab)
“Each patient’s baseline AND matched external comparator arm together provide robust control data to assess treatment effect” (opens the source at this quote in a new tab)

Matching variables and selection rules for the external control arm

No evidence found.

Statistical method for comparison with the pivotal trial

No evidence found.

Study results

No evidence found.

Source of the natural history comparison shown 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-A501-0223 is an observational cohort study with no study intervention, sponsored by Rocket Pharmaceuticals, the developer of RP-A501. No results are posted on the registry record and no results publication was identified; the one peer-reviewed document is a design abstract. The record estimates enrollment of 60 participants at 15 sites in 6 countries, the company reported more than 50 participants enrolled in August 2026, and the estimated primary completion date is December 2029, which is later than the June 2028 estimated primary completion of the pivotal trial. A subset of participants serves as the external control arm for a single-arm, open-label trial. The size of that subset, the rules for selecting it, the matching variables, and the statistical method of comparison have not been published; the September 2023 company presentation refers to “Appropriate matching” without naming variables. Eligibility differs between the two studies: the natural history study enrolls males aged 8 years and older and females aged 8 to 50 years, and its retrospective-only cohort requires prior cardiac transplantation or mechanical circulatory support, whereas the pivotal trial enrolls males aged 8 years and older with a left ventricular ejection fraction of at least 50%, New York Heart Association class II to III, and elevated high-sensitivity troponin I, and excludes prior transplantation. The primary outcome is left ventricular mass index by echocardiogram at months 12, 24, and 36, and part of the data is collected retrospectively from medical records; the design abstract states that retrospective records “include variable diagnostics/testing intervals”. The registered outcomes do not include myocardial LAMP2 protein expression, which is one of the two components of the pivotal trial's primary endpoint. The recruitment website states that a male participant may be referred from the natural history study to the gene therapy study. The Form 10-K filed in February 2026 states that the study “will serve as an external comparator”, and the Form 10-Q filed in August 2026 describes it as “running concurrently with the Phase 2 pivotal trial”. The natural history comparison shown in the October 2026 company presentation is attributed to “Unpublished data from International Danon Disease Registry”.