A Gene Therapy Study of RP-A501 in Male Patients 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 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.

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.

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.