Gene Therapy for Danon Disease

Not currently recruiting at 2 trial locations

Overseen By Clinical Information

Age: Any Age

Sex: Male

Trial Phase: Phase 1

Sponsor: Rocket Pharmaceuticals Inc.

Must not be taking: Positive inotropes, Vasodilators, Diuretics

Disqualifiers: Cardiac transplant, LVAD, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment, RP-A501, for Danon Disease, a rare genetic disorder affecting the heart and other systems. The study aims to determine the treatment's safety and understand its effects on the body. Participants will receive a single dose of the therapy through an IV. The study seeks males diagnosed with Danon Disease who have heart problems detectable on heart tests. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must be stable on oral medical therapy and not have received certain intravenous therapies in the 30 days before enrollment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that RP-A501, a gene therapy for Danon Disease, has promising safety results from earlier studies. In these studies, a single dose of RP-A501 was generally safe for patients. The treatment was well-tolerated, and participants reported heart improvement during the study. Although this information comes from early research, it provides a positive view of the therapy's safety for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike current treatments for Danon Disease, which mainly focus on managing symptoms and complications, RP-A501 aims to address the root cause by delivering a functional LAMP2B gene directly to patients' cells. This gene therapy uses a specially designed rAAV9 capsid to transport the human LAMP2B transgene, potentially correcting the genetic defect responsible for the disease. Researchers are excited about RP-A501 because it could offer a one-time treatment with long-lasting effects, providing a breakthrough for patients who currently have no curative options.

What evidence suggests that this gene therapy could be effective for Danon Disease?

Research has shown that RP-A501, the investigational gene therapy under study in this trial, could help treat Danon Disease. In previous studies, a single dose of this therapy led to the production of the LAMP2 protein in the heart and showed signs of improvement in patients. Over 4.5 years, patients remained stable, suggesting the treatment helped manage the disease. This therapy uses a virus to deliver a healthy gene, potentially correcting the genetic issue in Danon Disease. Early results are promising for improving heart function in patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Joseph W Rossano, M.D.

Principal Investigator

Children's Hospital of Philadelphia

Matthew Taylor, MD

Principal Investigator

University of Colorado, Anschutz Medical Ctr

Barry Greenberg, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for male patients with Danon Disease, a genetic condition affecting the heart and muscles. Participants must be males aged 8 years or older with cardiac involvement, able to walk over 150 meters unassisted, have normal blood counts and liver function, and not have had recent heart surgery or other serious health conditions.

Inclusion Criteria

Patients and/or competent custodial parents must provide informed written consent

I can walk more than 150 meters by myself in a walking test.

Your blood levels of hemoglobin, neutrophils, and platelets are within the normal range.

Exclusion Criteria

Your body has a high level of antibodies that can neutralize AAV9.

I have an active blood or solid organ cancer.

I have had a heart attack or unstable chest pain before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Administration of rituximab and sirolimus prophylactically before infusion of the investigational product

1 week

Treatment

Single intravenous infusion of RP-A501 gene therapy product

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Long-Term Follow-Up

Participants enter a long-term follow-up study for additional monitoring post-treatment

2 to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• RP-A501

Trial Overview The study tests RP-A501 gene therapy in males with Danon Disease. It's an open-label Phase 1 trial using AAV9.LAMP2B to deliver the LAMP2 gene. The goal is to assess safety and toxicity of this treatment in affected individuals without randomizing participants into different groups.

How Is the Trial Designed?

Group I: RP-A501 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Rocket Pharmaceuticals Inc.

Lead Sponsor

Trials

17

Recruited

430+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39556016/

Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon ... A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a period of 24 to ...

2. nejm.org nejm.org/doi/10.1056/NEJMoa2412392

Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon ... A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a ...

3. institut-myologie.org institut-myologie.org/en/2025/01/23/gene-therapy-improves-cardiomyopathy-in-danon-disease-results-of-an-initial-phase-i-trial/

Gene therapy improves cardiomyopathy in Danon disease Efficacy results: After a follow-up of 4.5 years, all patients were stable. The clinical efficacy of RP-A501, as assessed by cardiac ...

4. ir.rocketpharma.com ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-provides-update-phase-2-clinical-trial-rp

News Release Details The global, single-arm, multi-center Phase 2 pivotal trial evaluates the efficacy and safety of RP-A501 in 12 patients with Danon disease.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03882437

Study Details | NCT03882437 | Gene Therapy for Male ... 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) ...