for males ages 8 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion
Principal Investigator
by Barry Greenberg, MD
Photo of Barry Greenberg
Barry Greenberg



This is a non-randomized open-label Phase 1 study to evaluate the safety and toxicity of gene therapy using a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).

Official Title

A Clinical Study Evaluating a Recombinant Adeno-Associated Virus Serotype 9 (rAAV9) Capsid Containing the Human Lysosome-Associated Membrane Protein 2 Isoform B (LAMP2B) Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With DD


The study is a non-randomized open-label Phase I clinical trial to characterize the safety and toxicity associated with infusion of a recombinant adeno-associated serotype 9 (rAAV9) capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD). During the course of the study, approximately 11-23 subjects will receive a single intravenous (IV) infusion of the IP with each cohort receiving RP-A501 at sequentially higher dose levels. Three dose levels are planned to be investigated in 6 distinct cohorts. Prior to infusion of IP, rituximab and tacrolimus will be administered prophylactically. - Cohort 1: Age 15 -17 years: Low Dose (n=3 subjects) - Cohort 2: Age 15 - 17 years: Intermediate Dose (n=2-4) - Cohort 3: Age 15 - 17 years: High Dose (n=2-4) - Cohort 1A: Age 8 - 14 years: Low Dose (n=2-4) - Cohort 2A: Age 8 - 14 years : Intermediate Dose (n=2-4) - Cohort 3A: Age 8 - 14 years: High Dose (n=2-4) Pending determination of safety in the current cohort, concomitant enrollment in subsequent cohort is permissible. The study will also enable an initial evaluation of whether or not the IP results in cardiomyocyte and skeletal muscle transduction and gene expression and preliminary assessment of the extent of cardiomyocyte and histologic correction. Additionally, a preliminary evaluation of clinical stabilization following infusion will also be made.


Danon Disease hypertrophic cardiomyopathy HCM X-linked disease LAMP 2A Pediatric Skeletal myopathies Glycogen Storage Disease Type IIb


For males ages 8 years and up

Main Criteria for Inclusion:

The study will enroll adult and pediatric males with a confirmed diagnosis of DD. Patients may be of any race or ethnicity. Patients and/or competent custodial parents must provide informed written consent and meet all of the enrollment criteria as detailed subsequently to be eligible to participate.

  1. DD diagnosis with any confirmed LAMP2 mutation(s).
  2. Cardiac involvement as documented by at least one abnormal finding on electrocardiogram (ECG), echocardiogram, gadolinium-enhanced cardiac magnetic resonance imaging (MRI), or electrophysiology study.
  3. Age ≥15 years for cohorts 1, 2, and 3; 8-14 years for cohorts 1A, 2A, and 3A.
  4. Male gender.
  5. New York Heart Association (NYHA) Class II or III. Patients with NYHA Class I are eligible if unable to walk ≥450 meters during the 6-Minute Walk Test (6MWT).
  6. Adequate hematologic function as defined by:
  7. Hemoglobin ≥10 g/dL (6.2 mmol/L; Grade £1 anemia, per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0).
  8. Absolute neutrophil count ≥1,500/mm3 (1.5×109/L; Grade £1 neutropenia).
  9. Platelet count ≥75,000/mm3 (75×109/L; Grade £1 thrombocytopenia).
  10. Hepatic function as defined by:
  11. AST and ALT ≤10.0×ULN or GGT ≤2.0×ULN (transaminase elevations in DD are considered extensively to result from muscle injury; hence the relatively high upper limit for transaminases and consideration of GGT level, and the presence of additional hepatic eligibility markers of bilirubin and PT/INR).
  12. Serum bilirubin ≤1.5×ULN (i.e., Grade £1 bilirubin increase).
  13. PT/INR ≤1.5×ULN (in the absence of anticoagulation).
  14. Absence of cirrhosis on liver ultrasound
  15. Renal function as follows: creatinine ≤1.5×ULN; (if creatinine is >1.5×ULN, then creatinine clearance ≥50 mL/min/1.73m2 is required, as calculated by Modification of Diet in Renal Disease equation (Stevens 2006), the revised Schwartz formula (for patients under 18 years old) (Schwartz 2009), or 24-hour urine collection).
  16. Ability to provide informed consent (for adult patients and parents/legal guardians of pediatric patients) and assent (for patients age 15-17).
  17. . Ability to comply with study procedures including investigational therapy and follow-up evaluations.
  18. . Able to walk >150 meters unassisted during the 6MWT.
  19. . Patient has received meningococcal vaccination recommended by Centers for Disease Control as appropriate for age and health condition.

Main Criteria of Exclusion:

Patients meeting any of the following criteria are not eligible for study participation:

  1. IV therapy with positive inotropes, vasodilators, or diuretics within the 30 days prior to enrollment (i.e., patient must be stable on oral medical therapy).
  2. Prior cardiac transplantation or prior transplant of other organ (lung, liver, other).
  3. Cardiac surgery, percutaneous cardiac intervention, or valvuloplasty within 30 days prior to enrollment.
  4. Presence or requirement of a Left Ventricular Assisted Device (LVAD).
  5. Myocardial infarction, unstable angina, stroke, or transient ischemic attack (TIA) within 90 days prior to enrollment.
  6. Significant (greater than moderate) valvular stenosis or regurgitation on echocardiogram.
  7. Requires mechanical ventilation.
  8. Anti-AAV9 neutralizing antibody titer >1:40.
  9. Concurrent enrollment in any other clinical investigation involving use of an investigational agent for the treatment of CHF or cardiomyopathy.
  10. . Active hepatitis B or C infection (including patients with positive hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), or detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load). Patients with previous, adequately resolved HBV or HCV are eligible.
  11. . Significant medical conditions including documented human immunodeficiency virus (HIV) infection, active viral or other hepatitis, poorly-controlled hypertension or diabetes, poorly controlled cardiac arrhythmia, or uncontrolled viral, bacterial, or fungal infection.
  12. . Any concomitant medical or psychiatric condition that in the opinion of the Investigator renders the patient unfit for study participation or at higher than acceptable risk for study participation.
  13. . Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or other carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years.


  • University of California, San Diego accepting new patients
    La Jolla California 92037 United States
  • University of Colorado accepting new patients
    Aurora Colorado 80045 United States

Lead Scientist at UCSD


accepting new patients
Start Date
Completion Date
Rocket Pharmaceuticals Inc.
Phase 1
Study Type
Last Updated