RP-A501 gene therapy for males with Danon disease

Gene Therapy for Danon Disease: A Phase 2 Study Evaluating the Efficacy and Safety of Intravenously Administered Adeno-Associated Virus Serotype 9 (rAAV9) Vector Containing the Human LAMP2 Isoform B Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With Danon Disease

This gives a single IV dose of RP-A501 gene therapy to males aged 8 and older with Danon disease to see if it improves heart structure and symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (estimated)
• Ages: 8 Years and up
• Sex: Male
• Sponsor: Rocket Pharmaceuticals Inc. (Industry-sponsored)
• Locations: 6 sites (La Jolla, California and 5 other locations)
• Trial ID: NCT06092034 on ClinicalTrials.gov

What this trial studies

This single-arm Phase 2 trial delivers RP-A501 — an rAAV9 vector carrying the LAMP2B gene — as a one-time intravenous infusion to male patients aged 8 and older with genetically confirmed Danon disease. Eligible participants have left ventricular hypertrophy with preserved systolic function (LVEF ≥50%), NYHA class II–III symptoms, and elevated hsTnI, while those with high anti-AAV9 neutralizing antibodies or severe heart failure are excluded. The trial will track safety and signals of efficacy using cardiac imaging, biomarkers, and clinical follow-up at scheduled visits. The study is sponsored by Rocket Pharmaceuticals and enrolls at UC San Diego (La Jolla), Boston Children's Hospital (Boston), and Children's Hospital of Philadelphia (Philadelphia).

Who should consider this trial

Good fit: Ideal candidates are males aged 8 or older with a pathogenic or likely pathogenic LAMP2 variant, evidence of LV hypertrophy with LVEF ≥50%, NYHA class II–III symptoms, elevated hsTnI, and low anti-AAV9 neutralizing antibody titers.

Not a fit: Patients unlikely to benefit include females, children under 8, those with advanced heart failure or prior organ transplant, or those with high anti-AAV9 neutralizing antibody titers.

Why it matters

Potential benefit: If successful, RP-A501 could restore LAMP2B function and slow or reverse cardiomyopathy progression, improving heart function and symptoms in affected males.

How similar studies have performed: AAV9-based gene therapies have shown clinical success in other inherited diseases, but LAMP2B replacement for Danon disease is largely novel and has limited clinical data to date.

Eligibility criteria

Key Inclusion Criteria:

1. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.
2. Male.
3. Age ≥8 years.
4. Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following:

   1. Abnormal thickening of Left ventricular wall,
   2. Left ventricular ejection fraction (LVEF) ≥ 50%.
5. New York Heart Association (NYHA) Class II to III.
6. High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (ULN)
7. Ability to comply with study procedures including investigational therapy and follow-up evaluations.

Key Exclusion Criteria:

1. Anti-AAV9 neutralizing antibody titer \>1:40.
2. Severe heart failure or requirement for advanced therapies.
3. History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.
4. Prior cardiac or other organ (lung, liver, other) transplantation.

Where this trial is running

La Jolla, California and 5 other locations

• University of California, San Diego — La Jolla, California, United States (Recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
• German Heart Center Munich — Munich, Germany (Recruiting)
• Meyer Childrens Hospital — Florence, Italy (Recruiting)
• Great Ormund Street Hospital & UCL Institute of Cardiovascular Science — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Joseph Rossano, MD — Children's Hospital of Philadelphia
• Study coordinator: Clinical Information

Conditions Danon Disease; Hypertrophic Cardiomyopathy; HCM; X-linked disease; LAMP2; Pediatric; Skeletal Myopathies; Cardiomyopathy