In short
The drug DB-OTO-3 is being studied in clinical trials for its potential to treat genetic hearing loss in infants and children. This innovative gene therapy aims to address hearing loss caused by mutations in the otoferlin gene (OTOF). The trials are designed to evaluate the safety, tolerability, and effectiveness of DB-OTO-3 when administered through intracochlear injection.
At a glance
- Drug Name
- DB-OTO (consisting of DB-OTO-3 and DB-OTO-5)
- Trial Phase
- Phase 1/2
- Target Condition
- Congenital Hearing Loss due to otoferlin gene mutations
- Age Group
- Infants and children under 18 years
- Administration Method
- Intracochlear injection
- Primary Objective
- Evaluate safety and tolerability
- Secondary Objective
- Assess preliminary efficacy
- Key Inclusion Criteria
- Biallelic OTOF mutations, specific hearing loss criteria
- Key Exclusion Criteria
- Other hearing loss conditions, prior cochlear implants, history of certain medical conditions
- Primary Endpoint
- Incidence and severity of treatment-emergent adverse events
- Secondary Endpoints
- Changes in ABR thresholds, improvements in behavioral audiometry
What is DB-OTO?
DB-OTO is an innovative gene therapy being developed to treat a specific type of congenital hearing loss. This hearing loss is caused by mutations in a gene called otoferlin (OTOF). DB-OTO is designed to address the underlying genetic cause of this hearing loss, potentially offering a groundbreaking treatment option for affected individuals.
How Does DB-OTO Work?
DB-OTO is a complex therapy that uses two components to deliver a corrected version of the otoferlin gene to the inner ear:
- DB-OTO-5: This component carries the first part of the otoferlin gene.
- DB-OTO-3: This component carries the second part of the otoferlin gene.
Both components use a harmless virus called adeno-associated virus serotype 1 (AAV1) to deliver the genetic material. The therapy is designed to work specifically in hair cells of the inner ear, which are crucial for hearing. It uses a special "switch" (called a promoter) that ensures the gene is only active in these hair cells.
Who Can Benefit from DB-OTO?
DB-OTO is being developed for children and infants who have a specific type of genetic hearing loss. This hearing loss is caused by mutations in both copies of the otoferlin gene (called biallelic mutations). Otoferlin is a crucial protein for proper hearing function, and when it's not working correctly, it can lead to severe to profound hearing loss from birth.
The CHORD Clinical Trial
A clinical trial called CHORD (Phase 1/2) is currently underway to test DB-OTO. This trial aims to:
- Evaluate the safety and tolerability of DB-OTO in children and infants with otoferlin-related hearing loss
- Determine the best dose of DB-OTO
- Assess early signs of whether DB-OTO improves hearing
Eligibility Criteria
To participate in the CHORD trial, patients must meet specific criteria, including:
- Having mutations in both copies of the OTOF gene
- Being under 18 years old
- Having severe to profound hearing loss, as measured by specific hearing tests
- Not having certain other medical conditions or previous treatments that could interfere with the study
There are additional specific criteria for different age groups and other factors that the study team will evaluate.
What to Expect During the Trial
If a child participates in the CHORD trial, they will receive DB-OTO through a procedure called intracochlear injection. This means the therapy is injected directly into the cochlea, a part of the inner ear important for hearing.
The trial will start with treating one ear in a small group of patients. If this is found to be safe, the study may expand to treat both ears in more patients.
Throughout the trial, the research team will closely monitor participants for any side effects and will perform various tests to check if hearing improves.
Potential Benefits and Risks
While DB-OTO shows promise, it's important to remember that it's still being studied. Potential benefits could include improved hearing, but this is not guaranteed. As with any medical treatment, there may be risks and side effects. The research team will carefully monitor participants and provide detailed information about potential risks.
If you think your child might be eligible for this study, or if you want to learn more about DB-OTO, speak with your child's doctor or a genetic counselor. They can provide more information and help you understand if this potential treatment might be appropriate for your child.