Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B
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|ClinicalTrials.gov Identifier: NCT03882437|
Recruitment Status : Recruiting
First Posted : March 20, 2019
Last Update Posted : August 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Danon Disease||Biological: RP-A501||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
Evaluation of RP-A501 in pediatric patients (ages 8-14) will commence only pending determination of safety in the older (adult and age 15-17) population.
In Phase 1, RP-A501 will be investigated in three treatment cohorts, as follows with a single cohort currently recruiting:
Cohort 1: Adult and age 15-17: 6.7 × 1013 GC/kg (n=3-4)
Cohort 2: Adult and age 15-17: 1.1 × 1014 GC/kg (n=2 [patients already treated; closed for current enrollment])
Cohort 1A: Pediatric age 8-14: 6.7 × 1013 GC/kg (n=2-4)
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||April 17, 2019|
|Estimated Primary Completion Date :||October 21, 2022|
|Estimated Study Completion Date :||October 21, 2024|
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.
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.
- 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 ]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) [ Time Frame: 3 years ]Assessment of safety at both doses (single IV administration)
- Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy [ Time Frame: 3 years ]Assessment of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy
- Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing [ Time Frame: 3 years ]Assessment of clinical stabilization of cardiomyopathy following infusion of RP-A501 via cardiopulmonary testing
- Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology [ Time Frame: 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 [ Time Frame: 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.
- Determination and characterization of immunologic response to RP-A501 [ Time Frame: 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 [ Time Frame: 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.
- Evaluation of overall survival [ Time Frame: 3 years ]Assessment of overall survival post RP-A501
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03882437
|Contact: Clinical Information||+1 646-627-0033||Danonclinicaltrial@rocketpharma.com|
|United States, California|
|University of California, San Diego||Recruiting|
|La Jolla, California, United States, 92037|
|Contact: Barry Greenberg, MD|
|United States, Colorado|
|University of Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Matthew Taylor, MD, PhD|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Joseph Rossano, MD|
|Principal Investigator:||Joseph Rossano, MD||Children's Hospital of Philadelphia|
|Principal Investigator:||Matthew Taylor, MD, PhD||University of Colorado, Anschutz Medical Ctr|
|Principal Investigator:||Barry Greenberg, MD||University of California, San Diego|