#1 Clinical Trials Search in Europe

Adeno-Associated Virus Serotype 9 Vector Containing The Human Lamp2 Isoform B Transgene

A groundbreaking clinical trial is underway to assess the effectiveness and safety of a gene therapy treatment for Danon disease. This Phase 2 study focuses on using a specially designed virus, called AAV9.LAMP2B, to deliver a corrective gene to male patients with this rare genetic disorder. The therapy aims to improve heart function and quality of life for those affected by Danon disease.

Table of Contents

What is RP-A501 (AAV9.LAMP2B)?

RP-A501, also known as AAV9.LAMP2B, is a new gene therapy being developed to treat Danon disease. It is classified as an adeno-associated virus serotype 9 vector containing the human LAMP2 isoform B transgene.[1] This means it uses a harmless virus (AAV9) to deliver a healthy copy of the LAMP2B gene to cells in the body.

Some other names for this treatment include:[1]

  • Recombinant adeno-associated virus serotype 9 vector containing the human-lysosome-associated membrane glycoprotein 2 isoform B transgene
  • AAV9.LAMP2B

Target Disease: Danon Disease

RP-A501 is being developed to treat Danon disease, a rare genetic disorder that primarily affects the heart. Danon disease is caused by mutations in the LAMP2 gene, which leads to the buildup of cellular debris in various tissues, especially heart muscle cells.[1]

Symptoms of Danon disease often include:

  • Left ventricular hypertrophy: This means the left side of the heart becomes abnormally thick, making it harder for the heart to pump blood effectively.
  • Heart failure symptoms
  • Muscle weakness
  • Learning disabilities

How RP-A501 Works

RP-A501 is designed to work by delivering a functional copy of the LAMP2B gene to cells, particularly heart muscle cells. Here’s a simplified explanation of how it works:[1]

  1. The treatment is given through an intravenous infusion, which means it’s delivered directly into the bloodstream.
  2. The AAV9 virus, which carries the healthy LAMP2B gene, travels through the blood and enters cells, especially heart cells.
  3. Once inside the cells, the virus releases the healthy LAMP2B gene.
  4. The cells can then use this healthy gene to produce the LAMP2 protein, which is missing or defective in people with Danon disease.
  5. With the correct LAMP2 protein now present, the cells can better manage cellular waste, potentially improving heart function and reducing symptoms.

Clinical Trial Details

RP-A501 is currently being studied in a Phase 2 clinical trial. This means it has already shown promise in earlier studies and is now being tested in a larger group of patients to further evaluate its effectiveness and safety.[1]

The main goals of this clinical trial are:[1]

  • To see if RP-A501 can increase the amount of LAMP2 protein in heart tissue
  • To check if it can reduce left ventricular mass index (LVMI), which is a measure of heart enlargement
  • To assess its impact on quality of life and heart failure symptoms
  • To evaluate its safety

Eligibility Criteria

To participate in this clinical trial, patients must meet certain criteria. Some key requirements include:[1]

  • Being male (the trial is currently only for male patients)
  • Having a confirmed genetic diagnosis of Danon disease
  • Showing signs of left ventricular hypertrophy (thickened heart muscle)
  • Having heart failure symptoms classified as New York Heart Association (NYHA) Class II to III
  • Having elevated levels of a heart damage marker called high-sensitivity troponin I (hsTnI)

There are also several conditions that would prevent someone from participating in the trial, such as having certain heart complications or having received a previous organ transplant.[1]

Potential Benefits

If successful, RP-A501 could potentially offer several benefits for patients with Danon disease:[1]

  • Improved heart function by reducing heart muscle thickening
  • Reduced levels of biomarkers that indicate heart damage
  • Better quality of life and fewer heart failure symptoms
  • Increased survival without major heart events (like need for heart transplant or hospitalization for heart failure)

Safety Considerations

As with any new treatment, safety is a crucial consideration. The clinical trial is carefully monitoring for any side effects or safety issues. Some specific safety measures include:[1]

  • Checking for antibodies against the AAV9 virus before treatment
  • Monitoring for any adverse events during and after treatment
  • Assessing the long-term safety of the treatment

It’s important to note that as this is an experimental treatment, all potential risks may not be known yet. Patients considering participating in the trial should discuss all potential risks and benefits with their healthcare providers and the study team.

Aspect Details
Trial Name Gene Therapy for Danon Disease: Phase 2 Study of RP-A501 (AAV9.LAMP2B)
Main Objective Evaluate improvement in LAMP2 myocardial tissue expression and left ventricular mass index (LVMI)
Treatment RP-A501 (AAV9.LAMP2B) administered via intravenous infusion
Eligible Participants Male patients with confirmed Danon disease, left ventricular hypertrophy, and NYHA Class II-III symptoms
Key Endpoints LAMP2 protein expression, LVMI, heart failure biomarkers, quality of life, event-free survival
Safety Monitoring Incidence, severity, and duration of treatment-emergent safety events

FAQ

  • What is Danon disease? Danon disease is a rare genetic disorder that primarily affects the heart, causing thickening of the heart muscle (hypertrophic cardiomyopathy) and other complications. It is caused by mutations in the LAMP2 gene.
  • What is the purpose of this clinical trial? The main goal of this trial is to evaluate whether the gene therapy treatment AAV9.LAMP2B can significantly improve heart function in male patients with Danon disease. Researchers will measure this by looking at LAMP2 protein expression in heart tissue and changes in left ventricular mass index (LVMI).
  • How is the gene therapy administered? The gene therapy, called RP-A501 or AAV9.LAMP2B, is administered through intravenous infusion. This means it is delivered directly into the bloodstream.
  • Who is eligible to participate in this trial? Eligible participants are male patients with a confirmed genetic diagnosis of Danon disease, evidence of left ventricular hypertrophy with preserved heart function, and New York Heart Association (NYHA) Class II to III heart failure symptoms. They must also have elevated levels of a specific heart injury marker (hsTnI).
  • What are the potential benefits and risks of participating in this trial? Potential benefits include improved heart function and quality of life. However, as with any clinical trial, there may be risks and side effects. The study will closely monitor participants for any treatment-related safety events. It's important to discuss potential risks and benefits with the research team and your healthcare provider.

Ongoing Clinical Trials on Adeno-Associated Virus Serotype 9 Vector Containing The Human Lamp2 Isoform B Transgene

  • Study on Gene Therapy with AAV9.LAMP2B for Male Patients with Danon Disease

    Recruiting

    2 1 1 1
    Investigated drugs:
    Germany Italy

Glossary

  • Danon disease: A rare genetic disorder caused by mutations in the LAMP2 gene, primarily affecting the heart and causing thickening of the heart muscle (hypertrophic cardiomyopathy).
  • Gene therapy: A treatment approach that involves introducing genetic material into a person's cells to treat or prevent disease.
  • AAV9.LAMP2B (RP-A501): The gene therapy product used in this trial, consisting of an adeno-associated virus serotype 9 vector containing the human LAMP2 isoform B gene.
  • LAMP2: Lysosome-associated membrane glycoprotein 2, the gene affected in Danon disease.
  • Left ventricular mass index (LVMI): A measure of heart muscle thickness, used to assess the severity of heart muscle enlargement.
  • Hypertrophic cardiomyopathy: A condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood.
  • New York Heart Association (NYHA) Class: A classification system for heart failure symptoms, ranging from Class I (no symptoms) to Class IV (severe symptoms).
  • hsTnI: High-sensitivity troponin I, a biomarker used to detect heart muscle injury.
  • Intravenous infusion: A method of administering medication or fluids directly into a vein.
  • Phase 2 trial: A stage of clinical research that aims to assess the effectiveness and side effects of a new treatment in a larger group of patients.

References

  1. http://clinicaltrials.eu/trial/study-on-gene-therapy-with-aav9-lamp2b-for-male-patients-with-danon-disease/