A Multi-Center, Open Label Gene Therapy Study of RP-A501 in Male Patients With Danon Disease

Gene Therapy for Danon Disease: A Phase 2 Study Evaluating the Efficacy and Safety of Intravenously Administered Adeno-Associated Virus Serotype 9 (rAAV9) Vector Containing the Human LAMP2 Isoform B Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With Danon Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Danon Disease
• Intervention / Treatment: Genetic: RP-A501

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Information; Phone Number: 646-627-0033; Email: clinicaltrials@rocketpharma.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California, San Diego
      • Contact: Barry Greenberg, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Joseph Rossano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.
2. Male gender.
3. Age ≥8 years.

4. Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following:

   1. For subjects < 18 years, z-score of the left ventricular posterior wall or interventricular septum at end diastole ≥+ 2, and for subjects ≥18 years, left ventricular posterior wall or interventricular septum at end diastole >13 mm (>12 mm if family history of clinically significant Danon disease),
   2. Left ventricular ejection fraction (LVEF) ≥ 50%.
5. New York Heart Association (NYHA) Class II to III.
6. hsTnI ≥20% above the 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. Intravenous inotropic, vasodilator, or diuretic therapy within the 30 days prior to enrollment.
3. Presence or requirement for mechanical circulatory support (MCS).
4. Presence or requirement for mechanical ventilation.
5. History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.
6. Prior cardiac or other organ (lung, liver, other) transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RP-A501; One planned dose of RP-A501 in cohorts of subjects with a confirmed diagnosis of Danon Disease.	Genetic: 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 IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-Primary endpoint including myocardial tissue expression of LAMP2 protein and decrease in left ventricular mass index (LVMI).	Evaluation of efficacy associated with RP-A501	12 Months post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LAMP2 protein expression	Evaluation of efficacy associated with RP-A501	12 months post infusion
LVMI	Evaluation of efficacy associated with RP-A501	12 months post infusion
hsTnI	Evaluation of efficacy associated with RP-A501	12 months post infusion
NT-proBNP	Evaluation of efficacy associated with RP-A501	12 months post infusion
KCCQ and NYHA class	Evaluation of efficacy associated with RP-A501	12 months post infusion
Event free survival with events defined as death, heart transplant, mechanical circulatory support (MCS) or heart failure hospitalization.	Evaluation of efficacy associated with RP-A501	60 months post infusion
Incidence, severity and duration of treatment emergent safety events.	Evaluation of safety	60 months post infusion

Collaborators and Investigators

• Sponsor: Rocket Pharmaceuticals Inc.
• Investigators: Principal Investigator: Joseph Rossano, MD, Children's Hospital of Philadelphia; Principal Investigator: Barry Greenberg, MD, University of California San Diego (UCSD)

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Cardiomyopathy; Hypertrophic Cardiomyopathy; HCM; Lysosomal Storage Disorder; X-linked disease; LAMP2; Skeletal Myopathies
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Cardiomyopathies; Glycogen Storage Disease; Glycogen Storage Disease Type IIb
• Other Study ID Numbers: RP-A501-0123

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No