Gene Therapy for Danon Disease

Recruiting at 5 trial locations

Overseen By Clinical Information

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Rocket Pharmaceuticals Inc.

Disqualifiers: Severe heart failure, Thrombosis, Transplantation, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy, RP-A501, to determine its effectiveness in treating Danon Disease, a rare genetic disorder affecting the heart. Researchers aim to assess the safety and efficacy of this treatment in males with Danon Disease. The trial seeks males with a confirmed genetic marker for Danon Disease, noticeable thickening of the heart wall, and the ability to manage daily activities, albeit with some limitations due to heart issues. Participants must be able to follow study procedures and attend follow-up visits. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that RP-A501 is likely to be safe for humans?

Research has shown that RP-A501 has been safe in earlier studies. In one study, a single dose of RP-A501 was safe and improved heart function. Patients generally tolerated the treatment well, and all remained stable for over four years. This suggests that RP-A501 could be a safe option for people with Danon Disease. However, like any treatment, risks may exist, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RP-A501 is unique because it offers a gene therapy approach for Danon Disease, which is a departure from the current treatments that mainly focus on managing symptoms. Most treatments for this condition involve medications that aim to control heart symptoms or delay the progression of heart failure, but they do not address the root cause. RP-A501 works by delivering a healthy copy of the LAMP2 gene directly into the patient's cells, potentially correcting the underlying genetic defect. This novel approach has the potential to not only improve symptoms but also alter the disease's course by tackling its genetic roots, which is why researchers are excited about its possibilities.

What evidence suggests that RP-A501 might be an effective treatment for Danon Disease?

Research has shown that RP-A501, the investigational gene therapy studied in this trial, might improve heart function in people with Danon Disease. In earlier studies, patients who received a single dose demonstrated improved heart function and higher levels of LAMP2, a protein crucial for heart health. After 4.5 years, patients remained stable, indicating long-lasting benefits. Some side effects occurred but were manageable or resolved. These findings suggest RP-A501 could effectively treat Danon Disease. ^{2 4 6 7 8}

Who Is on the Research Team?

Joseph W Rossano, M.D.

Principal Investigator

Children's Hospital of Philadelphia

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 rare genetic condition. Participants must have a specific gene mutation, good heart pump function (LVEF ≥ 50%), elevated heart stress levels (hsTnI), be at least 8 years old, show signs of thickened heart muscle but normal pumping ability, and be able to follow the study's procedures. They should not need mechanical breathing support or have had certain serious cardiovascular events.

Inclusion Criteria

I am 8 years old or older.

You have a specific heart condition called left ventricular hypertrophy with preserved systolic function.

Your heart is pumping blood normally.

Exclusion Criteria

I have had a stroke, heart attack, or other serious heart-related issues.

I have had a heart, lung, liver, or other organ transplant.

You are currently using or need a machine to help you breathe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of RP-A501

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits as per protocol

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

60 months

What Are the Treatments Tested in This Trial?

Interventions

• RP-A501

Trial Overview The trial is testing RP-A501, a gene therapy delivered via a virus vector designed to introduce a healthy version of the LAMP2B gene into patients' cells. It aims to assess how effective and safe this treatment is in improving symptoms or halting progression of Danon Disease in males.

How Is the Trial Designed?

Group I: RP-A501 Experimental Treatment 1 Intervention

One planned dose of RP-A501 in cohorts of subjects with a confirmed diagnosis of Danon Disease.

Who Is Running the Clinical Trial?

Rocket Pharmaceuticals Inc.

Lead Sponsor

Trials

17

Recruited

430+

Published Research Related to This Trial

Gene therapy using a recombinant adenoviral vector to deliver the human PAH gene effectively normalized phenylalanine levels in PAH-deficient mice within one week, showcasing the potential for treating classical phenylketonuria (PKU).

The study found that achieving only 10-20% of normal PAH enzyme activity in the liver was enough to restore normal serum phenylalanine levels, indicating that even partial restoration of enzyme function could be therapeutically beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer. Fang, B., Eisensmith, RC., Li, XH., et al.[2012]

AAV-mediated gene therapy using a human codon-optimized GAA gene can promote immune tolerance in a mouse model of Pompe disease, potentially improving treatment outcomes by reducing immune responses that limit efficacy.

The combination of AAV9 constructs targeting both liver and muscle tissues not only enhances enzyme expression but also expands regulatory T-cells, which can prevent allergic reactions to enzyme replacement therapy, suggesting a promising dual approach for treating Pompe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease. Doerfler, PA., Todd, AG., Clément, N., et al.[2018]

AAV8-PAL gene therapy effectively corrected high phenylalanine levels in both male and female PKU mice, demonstrating long-term efficacy after a single intravenous treatment.

The therapy showed no significant liver injury, indicating a safe approach for potential treatment of phenylketonuria (PKU) in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase. Tao, R., Xiao, L., Zhou, L., et al.[2022]

The study demonstrated that using a synthetic AAV vector (Anc80) to deliver a functional copy of the PAH gene in a mouse model of PKU resulted in a significant and lasting reduction of phenylalanine levels, indicating effective restoration of metabolic function.

Administration of the AAV vector was safe, with no serious adverse effects observed even at the highest tested dose, and only minor, transient changes in liver enzymes, suggesting a promising approach for gene therapy in PKU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of an adeno-associated virus serotype Anc80 to provide durable cure of phenylketonuria in a mouse model. Kaiser, RA., Weber, ND., Trigueros-Motos, L., et al.[2022]

Gene therapy using AAV vectors to deliver the RPE65 gene has been shown to be safe and effective for treating Leber's congenital amaurosis (LCA), with positive effects on retinal and visual function lasting at least 1.5 years in patients.

The treatment did not trigger significant immune responses against the RPE65 protein, indicating that AAV-mediated gene transfer can maintain its therapeutic effects without causing harm to the retinal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration. Simonelli, F., Maguire, AM., Testa, F., et al.[2022]

Citations

1. ir.rocketpharma.com ir.rocketpharma.com/news-releases/news-release-details/rocket-pharmaceuticals-announces-fda-has-lifted-clinical-hold

Rocket Pharmaceuticals Announces FDA Has Lifted the ... RP-A501 has the potential to restore or stabilize cardiac function in patients with Danon disease. RP-A501 consists of a recombinant adeno- ...

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06092034

NCT06092034 | A Gene Therapy Study of RP-A501 in ... 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 ...

4. 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 ...

5. ir.rocketpharma.com ir.rocketpharma.com/node/12141/pdf

Publication of Phase 1 RP-A501 Long-Term Data and ... All RP-A501 or immunomodulatory regimen-related AEs were manageable or reversible. One patient had worsening heart failure at baseline (LVEF < ...

6. 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.

7. nejm.org nejm.org/doi/abs/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 period of 24 to ...

8. cgtlive.com cgtlive.com/view/gene-therapy-rpa501-promising-phase-1-results-danon-disease

Gene Therapy RP-A501 Shows Promising Phase 1 Results ... Safety Profile. The therapy was deemed generally well-tolerated, with all patients alive and in stable condition after more than 4 years of ...