Danon Disease
Conditions
Keywords
Hypertrophic Cardiomyopathy, HCM, X-linked disease, LAMP2, Pediatric, Skeletal Myopathies, Cardiomyopathy, Lysosomal Storage Disorder, Left Ventricular Hypertrophy
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.
Interventions
GENETICRP-A501
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.
Sponsors
Rocket Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of efficacy via 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
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of efficacy via components of the primary endpoint - LAMP2 | 12 months post infusion | Increase in LAMP2 protein expression |
| Evaluation of efficacy via components of the primary endpoint - Left Ventricular Mass Index (LVMI) | 12 months post infusion | Decrease in Left Ventricular Mass Index (LVMI) |
| Evaluation of efficacy via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI) | 12 months post infusion | Decrease in high sensitivity Troponin I (hsTnI) |
| Evaluation of efficacy 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 via assessment of event-free survival | 60 months post infusion | 1. Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization 2. Incidence of death, heart transplant, MCS, or heart failure hospitalization |
| Evaluation of safety | 60 months post infusion | Incidence, severity and duration of treatment emergent safety events. |
Countries
Germany, Italy, United Kingdom, United States
Contacts
CONTACTClinical Information
PRINCIPAL_INVESTIGATORJoseph Rossano, MD
Children's Hospital of Philadelphia
PRINCIPAL_INVESTIGATORBarry Greenberg, MD
University of California, San Diego
Outcome results
None listed