A Multi-Center, Open Label Gene Therapy Study of RP-A501 in Male Patients With Danon Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Danon Disease

Intervention / Treatment
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* Genetic: RP-A501


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene. Male gender. Age ≥8 years. Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following: For subjects < 18 years, z-score of the left ventricular posterior wall or interventricular septum at end diastole ≥+ 2, and for subjects ≥18 years, left ventricular posterior wall or interventricular septum at end diastole >13 mm (>12 mm if family history of clinically significant Danon disease), Left ventricular ejection fraction (LVEF) ≥ 50%. New York Heart Association (NYHA) Class II to III. hsTnI ≥20% above the ULN Ability to comply with study procedures including investigational therapy and follow-up evaluations. Key Exclusion Criteria: Anti-AAV9 neutralizing antibody titer >1:40. Intravenous inotropic, vasodilator, or diuretic therapy within the 30 days prior to enrollment. Presence or requirement for mechanical circulatory support (MCS). Presence or requirement for mechanical ventilation. History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina. Prior cardiac or other organ (lung, liver, other) transplantation.

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RP-A501<br>One planned dose of RP-A501 in cohorts of subjects with a confirmed diagnosis of Danon Disease. | Genetic: RP-A501<br>* RP-A501 is a gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-Primary endpoint including myocardial tissue expression of LAMP2 protein and decrease in left ventricular mass index (LVMI). | Evaluation of efficacy associated with RP-A501 | 12 Months post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LAMP2 protein expression | Evaluation of efficacy associated with RP-A501 | 12 months post infusion | 
| LVMI | Evaluation of efficacy associated with RP-A501 | 12 months post infusion | 
| hsTnI | Evaluation of efficacy associated with RP-A501 | 12 months post infusion | 
| NT-proBNP | Evaluation of efficacy associated with RP-A501 | 12 months post infusion | 
| KCCQ and NYHA class | Evaluation of efficacy associated with RP-A501 | 12 months post infusion | 
| Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization. | Evaluation of efficacy associated with RP-A501 | 60 months post infusion | 
| Incidence, severity and duration of treatment emergent safety events. | Evaluation of safety | 60 months post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertrophic Cardiomyopathy, HCM, X-linked disease, LAMP2, Pediatric, Skeletal Myopathies, Cardiomyopathy, Lysosomal Storage Disorder