Clinical trial NCT06092034: A Gene Therapy Study of RP-A501 in Male Patients With Danon Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Danon Disease
Keywords: Hypertrophic Cardiomyopathy
HCM
X-linked disease
LAMP2
Pediatric
Skeletal Myopathies
Cardiomyopathy
Lysosomal Storage Disorder
Left Ventricular Hypertrophy
Lead sponsor: Rocket Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 12
Sex: MALE
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Key Inclusion Criteria:

1. Documentation of a pathogenic or likely pathogenic variant of the LAMP2 gene.
2. Male.
3. Age ≥8 years.
4. Evidence of left ventricular hypertrophy with preserved systolic function phenotype as defined by each of the following:

   1. Abnormal thickening of Left ventricular wall,
   2. Left ventricular ejection fraction (LVEF) ≥ 50%.
5. New York Heart Association (NYHA) Class II to III.
6. High sensitivity Troponin I (hsTnI) ≥20% above the upper limit of normal (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. Severe heart failure or requirement for advanced therapies.
3. History of intracardiac thrombosis or arterial thromboembolic events including stroke, transient ischemic attack (TIA), acute coronary syndrome, myocardial infarction or unstable angina.
4. Prior cardiac or other organ (lung, liver, other) transplantation.

Primary outcomes:
measure: Evaluation of efficacy associated with RP-A501 via co-primary endpoint comprised of LAMP2 myocardial tissue expression and left ventricular mass index
timeFrame: 12 Months post-infusion
Secondary outcomes:
measure: Evaluation of efficacy associated with RP-A501 via components of the co-primary endpoint - LAMP2
timeFrame: 12 months post infusion
measure: Evaluation of efficacy associated with RP-A501 via components of the co-primary endpoint - Left Ventricular Mass Index (LVMI)
timeFrame: 12 months post infusion
measure: Evaluation of efficacy associated with RP-A501 via biomarker evidence of myocardial injury - High Sensitivity Troponin I (hsTnI)
timeFrame: 12 months post infusion
measure: Evaluation of efficacy associated with RP-A501 via biomarker evidence of myocardial injury - N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
timeFrame: 12 months post infusion
measure: Evaluation of efficacy associated with RP-A501 via assessment of event-free survival
timeFrame: 60 months post infusion
measure: Evaluation of safety associated with RP-A501
timeFrame: 60 months post infusion
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Munich
country: Germany
facility: German Heart Center Munich
city: Florence
country: Italy
facility: Meyer Childrens Hospital
city: London
country: United Kingdom
facility: Great Ormund Street Hospital & UCL Institute of Cardiovascular Science
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Joseph Rossano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Barry Greenberg, MD
role: PRINCIPAL_INVESTIGATOR
References: