A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease

Phase 2

Recruiting

• Conditions: Danon Disease
• Interventions: Genetic: RP-A501

• Registration Number: NCT06092034
• Lead Sponsor: Rocket Pharmaceuticals Inc.

Brief Summary

This is a single arm Phase 2 trial to evaluate the efficacy and safety of RP-A501, a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene, in male patients with Danon Disease.

Detailed Description

The study is a single arm Phase 2 clinical trial to characterize the safety and efficacy of RP-A501, a recombinant adeno-associated serotype 9 (rAAV9 capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene) in male patients with Danon Disease.

Male subjects ≥8 years of age will receive a single intravenous infusion of RP-A501.

Study Timeline

• Study Start: 2023-09-05
• Study First Submitted: 2023-10-11
• Study First Submitted QC: 2023-10-17
• Study First Posted: 2023-10-23
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-10
• Primary Completion: 2025-09
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 12

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RP-A501	RP-A501	One planned dose of RP-A501 in cohorts of subjects with a confirmed diagnosis of Danon Disease.

Primary Outcome Measures

Name	Time	Method
Evaluation of efficacy associated with RP-A501 via co-primary endpoint comprised of LAMP2 myocardial tissue expression and left ventricular mass index	12 Months post-infusion	Increase of myocardial tissue expression of LAMP2 protein and decrease in left ventricular mass index (LVMI).

Secondary Outcome Measures

Name	Time	Method
Evaluation of efficacy associated with RP-A501 via components of the co-primary endpoint - Left Ventricular Mass Index (LVMI)	12 months post infusion	Decrease in Left Ventricular Mass Index (LVMI)
Evaluation of efficacy associated with RP-A501 via biomarker evidence of myocardial injury - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)	12 months post infusion	Decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
Evaluation of efficacy associated with RP-A501 via assessment of event-free survival	60 months post infusion	Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization and incidence of death, heart transplant, MCS, or heart failure hospitalization from baseline to 60 months post RP-A501 infusion.
Evaluation of efficacy associated with RP-A501 via components of the co-primary endpoint - LAMP2	12 months post infusion	Increase in LAMP2 protein expression
Evaluation of efficacy associated with RP-A501 via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI)	12 months post infusion	Decrease in high sensitivity Troponin I (hsTnI)
Evaluation of safety associated with RP-A501	60 months post infusion	Incidence, severity and duration of treatment emergent safety events.

Trial Locations

Locations (6)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Meyer Childrens Hospital; 🇮🇹 Florence, Italy

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

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

German Heart Center Munich; 🇩🇪 Munich, Germany

Great Ormund Street Hospital & UCL Institute of Cardiovascular Science; 🇬🇧 London, United Kingdom