#1 Clinical Trials Search in Europe

Db-Oto-3

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.

Table of Contents

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)[1]. 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:

  1. DB-OTO-5: This component carries the first part of the otoferlin gene.
  2. 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[1]. 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[1].

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)[1]. 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[1]. 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[1]
  • Being under 18 years old[1]
  • Having severe to profound hearing loss, as measured by specific hearing tests[1]
  • Not having certain other medical conditions or previous treatments that could interfere with the study[1]

There are additional specific criteria for different age groups and other factors that the study team will evaluate[1].

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[1].

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[1].

Throughout the trial, the research team will closely monitor participants for any side effects and will perform various tests to check if hearing improves[1].

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[1].

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.

Aspect Details
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

FAQ

  • What is DB-OTO-3? DB-OTO-3 is part of a gene therapy called DB-OTO. It is one of two components (along with DB-OTO-5) that work together to potentially treat genetic hearing loss caused by mutations in the otoferlin gene.
  • Who can participate in these clinical trials? The trials are open to children under 18 years of age who have been diagnosed with hearing loss due to mutations in both copies of their otoferlin gene. Participants must meet specific hearing criteria and other health requirements.
  • How is DB-OTO-3 administered? DB-OTO-3 is given through an intracochlear injection, which means it is injected directly into the inner ear (cochlea).
  • What are the main goals of these clinical trials? The primary goals are to evaluate the safety and tolerability of DB-OTO in children and infants. The trials also aim to assess the preliminary effectiveness of the treatment in improving hearing.
  • Are there any risks associated with participating in these trials? As with all clinical trials, there may be risks involved. The trials are designed to monitor for any adverse events, both systemic (affecting the whole body) and local (affecting the ear). Specific risks will be discussed with participants and their families before enrollment.

Ongoing Clinical Trials on Db-Oto-3

  • Study on DB-OTO for Safety and Tolerability in Infants and Children with Genetic Hearing Loss

    Recruiting

    2 1 1
    Investigated drugs:
    Germany Spain

Glossary

  • Otoferlin (OTOF): A gene that plays a crucial role in hearing. Mutations in this gene can cause congenital hearing loss.
  • Intracochlear injection: A method of delivering medication directly into the cochlea, which is part of the inner ear responsible for hearing.
  • Gene therapy: A technique that uses genes to treat or prevent disease. In this case, it involves introducing functional copies of the otoferlin gene to address hearing loss.
  • Adeno-associated viral (AAV) vector: A tool used in gene therapy to deliver genetic material into cells. It's derived from a virus but modified to be safe for therapeutic use.
  • Auditory Brainstem Response (ABR): A test that measures the brain's response to sound, used to assess hearing function, especially in infants and young children.
  • Otoacoustic emissions (OAE): Sounds produced by the inner ear, either spontaneously or in response to stimuli. Their presence indicates that certain parts of the hearing mechanism are working.
  • Cochlear microphonic: An electrical signal generated by hair cells in the cochlea in response to sound, which can be measured to assess cochlear function.
  • Decibel (dB): A unit used to measure the intensity of sound. In hearing tests, it's often expressed as dB HL (Hearing Level) or dB nHL (normal Hearing Level).
  • Pure-tone audiometry: A hearing test that uses different frequencies and intensities of sound to determine the softest sounds a person can hear.
  • Speech awareness threshold (SAT): The lowest level at which a person can detect the presence of speech sounds.
  • Speech reception threshold (SRT): The lowest level at which a person can correctly identify 50% of simple speech words.

References

  1. http://clinicaltrials.eu/trial/study-on-db-oto-for-safety-and-tolerability-in-infants-and-children-with-genetic-hearing-loss/