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

Danon Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06092034
• Other study ID #: RP-A501-0123
• Status: Recruiting
• Phase: Phase 2
• Start date: September 5, 2023
• Est. completion date: September 2029

Study information

• Verified date: September 2023
• Source: Rocket Pharmaceuticals Inc.
• Contact: Clinical Information
• Phone: 646-627-0033
• Email: clinicaltrials[@]rocketpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: September 2029
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 8 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Danon Disease

Intervention

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.

Locations

Country	Name	City	State
United States	University of California, San Diego	La Jolla	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Rocket Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	LAMP2 protein expression	Evaluation of efficacy associated with RP-A501	12 months post infusion
Secondary	LVMI	Evaluation of efficacy associated with RP-A501	12 months post infusion
Secondary	hsTnI	Evaluation of efficacy associated with RP-A501	12 months post infusion
Secondary	NT-proBNP	Evaluation of efficacy associated with RP-A501	12 months post infusion
Secondary	KCCQ and NYHA class	Evaluation of efficacy associated with RP-A501	12 months post infusion
Secondary	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
Secondary	Incidence, severity and duration of treatment emergent safety events.	Evaluation of safety	60 months post infusion