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

Phase 1

Active, not recruiting

• Conditions: Danon Disease
• Interventions: Biological: RP-A501

• Registration Number: NCT03882437
• Lead Sponsor: Rocket Pharmaceuticals Inc.

Brief Summary

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).

Detailed Description

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 7-10 male subjects age 8 and over will receive a single intravenous (IV) infusion of the IP. Prior to infusion of IP, rituximab and sirolimus will be administered prophylactically.

All patients are planned to be followed for 36 months after investigational product administration. After the end of the follow-up period, patients will enter a Long-Term Follow-Up (LTFU) study enabling follow-up for an additional 2 to 5 years post-IP administration.

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.

Study Timeline

• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-03-18
• Study First Posted: 2019-03-20
• Study Start: 2019-04-17
• Status Verified: 2023-02
• Last Update Submitted: 2023-03-02
• Last Update Posted: 2023-03-03
• Primary Completion: 2025-03-24
• Study Completion: 2025-03-24

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 7

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RP-A501	RP-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 intravenous (IV) infusion. Subjects will receive one of three dose levels depending on the cohort.

Primary Outcome Measures

Name	Time	Method
Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy	3 years	Assessment of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy
Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)	3 years	Evaluation of safety associated with RP-A501
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)	3 years	Assessment of safety at both doses (single IV administration)
Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing	3 years	Assessment of clinical stabilization of cardiomyopathy following infusion of RP-A501 via cardiopulmonary testing

Secondary Outcome Measures

Name	Time	Method
Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology	3 years	Evaluation of sustained improvement or stabilization in cardiovascular pathophysiology as assessed by medical evaluation, radiographic evaluation of cardiac structure and function, and cardiopulmonary exercise/physiologic parameters
Determination of the percentage of patients in whom cardiomyocytes corrected LAMP2B gene and/or protein	3 years	Evaluation of the percentage of patients in whom cardiomyocytes contain the corrected LAMP2B gene and/or protein and improvement in DD-associated histologic abnormalities and when feasible to quantify the extent of genetic and histologic correction in the myocardium.
Evaluation of overall survival	3 years	Assessment of overall survival post RP-A501
Determination and characterization of immunologic response to RP-A501	3 years	Assessment of potential immunogenicity to the components of the investigational product
Determination of the percentage of patients who require and/or receive treatment for heart failure following RP-A501	3 years	Assessment of the percentage of patients who require and/or receive subsequent cardiac transplantation, left ventricular assist device (LVAD), implantable cardioverter-defibrillator or pacemaker placement, electrophysiologic ablative procedure for cardiac conduction aberrancy or subsequent hospitalizations for heart failure.

Trial Locations

Locations (3)

University of Colorado; 🇺🇸 Aurora, Colorado, United States

University of California, San Diego; 🇺🇸 La Jolla, California, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States