Overview
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.
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.
Eligibility
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.