Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B

• Register: ClinicalTrials.gov
• Last refreshed on: 13 March 2023
• Main ID: NCT03882437
• Date of registration: 12/03/2019
• Prospective Registration: Yes
• Primary sponsor: Rocket Pharmaceuticals Inc.
• Public title: Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B
• Scientific 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
• Date of first enrolment: April 17, 2019
• Target sample size: 7
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03882437
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Matthew Taylor, MD, PhD
• Affiliation: University of Colorado, Anschutz Medical Ctr

• Name: Joseph Rossano, MD
• Affiliation: Children's Hospital of Philadelphia

• Name: Barry Greenberg, MD
• Affiliation: University of California, San Diego

Key inclusion & exclusion criteria

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 and 2; 8-14 years for cohorts 1A.

4. Male gender.

5. New York Heart Association (NYHA) Class II or III.

6. Adequate hematologic function as defined by hemoglobin, absolute neutrophil count
(ANC), and platelet count = lower limit of normal (LLN).

7. Adequate hepatic function as defined by:

1. 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).

2. Serum bilirubin =1.2×ULN (i.e., Grade =1 bilirubin increase).

3. PT/INR =1.2×ULN (in the absence of anticoagulation).

4. Absence of cirrhosis or other signs of inflammation on liver ultrasound

8. Adequate renal function as defined by creatinine =ULN.

9. Ability to provide informed consent (for adult patients and parents/legal guardians of
pediatric patients) and assent (for patients age 15-17).

10. Ability to comply with study procedures including investigational therapy and
follow-up evaluations.

11. Able to walk >150 meters unassisted during the 6MWT.

12. Patient has received meningococcal vaccination recommended by Centers for Disease
Control as appropriate for age and health condition (vaccination must be performed at
least 6 weeks prior to IP administration).

Main Criteria of Exclusion:

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

1. I.V. 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. Prior cardiac surgery and/or percutaneous cardiac intervention for arteriothrombotic
complications, or valvuloplasty.

4. Presence or requirement of a Left Ventricular Assisted Device (LVAD).

5. History of intracardiac thrombosis or arteriothromboembolic events including stroke or
transient ischemic attack (TIA).

6. Left ventricular ejection fraction (LVEF) <40% at baseline.

7. History of the following prior arteriothromboembolic complications: myocardial
infarction or unstable angina.

8. Significant (greater than moderate) valvular stenosis or regurgitation on
echocardiogram.

9. Requires mechanical ventilation.

10. Anti-AAV9 neutralizing antibody titer >1:40.

11. Concurrent enrollment in any other clinical investigation involving use of an
investigational agent for the treatment of CHF or cardiomyopathy.

12. Active hepatitis B or C infection (including patients with positive hepatitis B
surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody
(HBcAb), or detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load).
Patients with previous, adequately resolved HBV or HCV are eligible.

13. 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.

14. 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.

15. 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.

16. Any contraindication to use of sirolimus which includes hypersensitivity to sirolimus
or HC-60 (polyoxyl 60 hydrogenated castor oil).

17. Active or latent tuberculosis.



Age minimum: 8 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Danon Disease

Intervention(s)

Biological: RP-A501

Primary Outcome(s)

Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy [Time Frame: 3 years]

Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE) [Time Frame: 3 years]

Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing [Time Frame: 3 years]

Number of participants within each dose level cohort with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE) [Time Frame: 3 years]

Secondary Outcome(s)

Determination of the percentage of patients who require and/or receive treatment for heart failure following RP-A501 [Time Frame: 3 years]

Determination of the percentage of patients in whom cardiomyocytes corrected LAMP2B gene and/or protein [Time Frame: 3 years]

Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology [Time Frame: 3 years]

Determination and characterization of immunologic response to RP-A501 [Time Frame: 3 years]

Evaluation of overall survival [Time Frame: 3 years]

Secondary ID(s)

RP-A501-0219

Source(s) of Monetary Support

Please refer to primary and secondary sponsors