#1 Clinical Trials Search in Europe

Adeno-Associated Viral Vector Serotype 8 Containing The 5′-Myo7A Gene Coding Sequence

This article discusses an ongoing clinical trial investigating the use of AAVB-081, a novel gene therapy treatment for Usher Syndrome Type 1B (USH1B) Retinitis Pigmentosa. AAVB-081 is an innovative approach using adeno-associated viral vectors to deliver the MYO7A gene, potentially addressing the underlying genetic cause of this rare inherited eye disorder. The trial aims to assess the safety, tolerability, and efficacy of this groundbreaking treatment, offering hope for patients with this debilitating condition.

Table of Contents

What is AAVB-081?

AAVB-081 is an innovative gene therapy product designed to treat a specific type of inherited eye disease[1]. It is also known by several other names, including Dual AAV8.MYO7A, AAV8.hMYO7A, AAV8.5′MYO7A, and AAV8.3′MYO7A. This therapy is currently being studied in clinical trials to evaluate its safety and effectiveness in treating patients with a condition called Usher Syndrome Type 1B (USH1B) Retinitis Pigmentosa.

Target Condition: Usher Syndrome Type 1B (USH1B) Retinitis Pigmentosa

Usher Syndrome Type 1B (USH1B) Retinitis Pigmentosa is a rare genetic disorder that affects both vision and hearing[1]. Patients with this condition experience progressive vision loss due to the degeneration of light-sensitive cells in the retina (the back part of the eye). This leads to a condition called retinitis pigmentosa, which can cause night blindness, loss of peripheral vision, and eventually severe visual impairment or blindness.

How AAVB-081 Works

AAVB-081 is a gene replacement therapy that uses a modified virus called adeno-associated virus serotype 8 (AAV8) to deliver a healthy copy of the MYO7A gene to the retina[1]. The MYO7A gene is responsible for producing a protein that is essential for the normal function of both the retina and the inner ear. In patients with USH1B, this gene is mutated, leading to vision and hearing problems.

The therapy consists of two components:

  1. AAV8.5′MYO7A: This contains the first part of the MYO7A gene.
  2. AAV8.3′MYO7A: This contains the second part of the MYO7A gene.

When both components are delivered to the retina, they work together to produce the full, functional MYO7A protein. This approach is called dual AAV8.MYO7A gene replacement[1].

Clinical Trial Details

A Phase 1/2 clinical trial is currently underway to study AAVB-081[1]. This trial is designed to:

  • Assess the safety and tolerability of AAVB-081 when administered subretinally (under the retina) in patients with USH1B retinitis pigmentosa
  • Determine the most appropriate dose that balances effectiveness and safety
  • Evaluate the effect of AAVB-081 on retinal anatomy and function using standard eye tests

The trial is open-label, which means both the researchers and participants know which treatment is being given. It also involves dose escalation, where different groups of patients receive increasing doses of the therapy to find the optimal amount.

Eligibility Criteria

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

  • Adults aged 18 to 50 years
  • Diagnosed with USH1B
  • Confirmed MYO7A gene mutations

Some exclusion criteria include:

  • History of retinal detachment
  • Poorly controlled diabetes
  • Pregnancy or breastfeeding
  • Previous participation in other gene therapy trials
  • Certain pre-existing eye conditions that could interfere with the treatment or study results

Safety and Effectiveness Measures

The trial will closely monitor participants for any side effects or adverse events. This includes[1]:

  • Physical examinations and vital signs checks
  • Blood and urine tests
  • Monitoring the body’s immune response to the therapy
  • Regular eye examinations, including vision tests, retinal imaging, and other specialized tests to assess eye health and function

Potential Benefits and Risks

While AAVB-081 shows promise in treating USH1B retinitis pigmentosa, it’s important to note that this is an experimental therapy still under investigation. Potential benefits may include improved retinal function and slowed progression of vision loss, but these are not guaranteed.

As with any medical treatment, there are potential risks. These may include side effects from the surgical procedure used to administer the therapy, immune reactions to the viral vector, or unexpected effects of the gene therapy itself. The clinical trial is designed to carefully monitor and assess these potential risks[1].

Aspect Details
Trial Name Study of Subretinally Injected AAVB-081 in Patients with Usher Syndrome Type IB (USH1B) Retinitis Pigmentosa
Trial Phase Phase 1/2 (Integrated)
Treatment AAVB-081 (Dual AAV8.MYO7A gene therapy)
Administration Subretinal injection
Target Condition Usher Syndrome Type 1B (USH1B) Retinitis Pigmentosa
Age Range 18 to 50 years
Primary Objectives Assess safety, tolerability, and determine optimal dose
Secondary Objective Evaluate effects on retinal anatomy and function
Key Inclusion Criteria Diagnosed USH1B, confirmed MYO7A mutations
Key Exclusion Criteria History of retinal detachment, poorly controlled diabetes, previous gene therapy
Primary Endpoints Incidence and severity of adverse events, number of dose-limiting toxicities

FAQ

  • What is AAVB-081 and how does it work? AAVB-081 is a gene therapy treatment that uses adeno-associated viral vectors (AAV8) to deliver the MYO7A gene to the retina. It consists of two parts: one containing the 5' end of the MYO7A gene and another containing the 3' end. This dual-vector approach aims to replace the faulty MYO7A gene in patients with Usher Syndrome Type 1B, potentially improving retinal function.
  • Who is eligible for this clinical trial? The trial is open to adults aged 18 to 50 with a confirmed molecular diagnosis of Usher Syndrome Type 1B due to MYO7A mutations. Participants must be willing to adhere to the study protocol and provide informed consent. However, there are several exclusion criteria, such as a history of retinal detachment or poorly controlled diabetes.
  • How is AAVB-081 administered? AAVB-081 is administered through subretinal injection. This means the treatment is delivered directly into the space beneath the retina, allowing for targeted delivery of the gene therapy to the affected cells.
  • What are the main objectives of this clinical trial? The primary objectives are to assess the safety and tolerability of subretinal administration of AAVB-081 in patients with USH1B retinitis pigmentosa, and to determine a well-tolerated dose with an optimal risk-benefit profile. The trial also aims to evaluate the effect of AAVB-081 on retinal anatomy and function using standardized diagnostic tests.
  • What are the potential risks and side effects of this treatment? As this is a Phase 1/2 trial, the full range of potential risks and side effects is not yet known. The study will closely monitor for adverse events, including serious adverse events and dose-limiting toxicities. Participants will undergo regular physical examinations, laboratory tests, and ophthalmic exams to assess safety. Potential risks may include immune responses to the viral vector or the MYO7A protein, as well as complications related to the subretinal injection procedure.

Ongoing Clinical Trials on Adeno-Associated Viral Vector Serotype 8 Containing The 5′-Myo7A Gene Coding Sequence

  • Study of AAVB-081 and Prednisolone for Patients with Usher Syndrome Type 1B Retinitis Pigmentosa

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

Glossary

  • Usher Syndrome Type 1B (USH1B): A rare genetic disorder characterized by hearing loss, vision loss due to retinitis pigmentosa, and balance problems. It is caused by mutations in the MYO7A gene.
  • Retinitis Pigmentosa: A group of inherited eye disorders that cause progressive vision loss due to the breakdown and loss of cells in the retina.
  • Adeno-Associated Viral Vector (AAV): A harmless virus modified to deliver genetic material into cells, commonly used in gene therapy.
  • MYO7A Gene: A gene that provides instructions for making a protein called myosin VIIA, which is important for the normal function of photoreceptors in the retina and hair cells in the inner ear.
  • Subretinal Injection: A medical procedure where a treatment is injected into the space beneath the retina.
  • Gene Therapy: A technique that uses genes to treat or prevent disease, often by replacing a faulty gene with a functional one.
  • Phase 1/2 Clinical Trial: An early-stage study that combines elements of both Phase 1 (focusing on safety and dosage) and Phase 2 (assessing effectiveness) trials.
  • Dose-Limiting Toxicity (DLT): Side effects of a treatment that are severe enough to prevent an increase in dosage or require a reduction in dosage.
  • Optical Coherence Tomography (OCT): A non-invasive imaging test that uses light waves to take cross-section pictures of the retina.
  • Electroretinogram (ERG): A test that measures the electrical responses of various cell types in the retina, including the photoreceptors (rods and cones).

References

  1. http://clinicaltrials.eu/trial/study-of-aavb-081-and-prednisolone-for-patients-with-usher-syndrome-type-1b-retinitis-pigmentosa/