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

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What is this study about?

This clinical trial is focused on studying congenital hearing loss caused by specific changes, known as mutations, in both copies of the Otoferlin gene (OTOF). The treatment being tested is called DB-OTO, which is an injection designed to help children and infants with this type of hearing loss. DB-OTO is made up of two parts, DB-OTO-5 and DB-OTO-3, which work together to deliver a gene that may help improve hearing.

The purpose of the study is to find the best dose of DB-OTO and to see how safe and well-tolerated it is in young patients. The study will start with a single injection in one ear and may later include injections in both ears. Participants will be monitored to see how they respond to the treatment and to check for any side effects. The study will also look at changes in hearing ability using tests that measure how well the brain responds to sound and how well participants can hear different tones and speech.

This trial is open-label, meaning that both the researchers and participants will know which treatment is being given. The study will take place over several years, allowing researchers to gather important information about the safety and effectiveness of DB-OTO in treating hearing loss due to OTOF mutations.

1 initial assessment

The trial begins with an initial assessment to confirm eligibility. This includes verifying the presence of mutations in both alleles of the OTOF gene and ensuring the patient is under 18 years of age.

Audiological tests are conducted to check for the absence of an auditory brainstem response (ABR) neural signal and the presence of otoacoustic emissions (OAE) or cochlear microphonic in the ear(s) to receive DB-OTO.

2 consent and preparation

Consent is obtained from a parent or legal guardian, and assent is provided by the participant if applicable.

The patient must be up-to-date with vaccinations according to the country-specific pediatric immunization schedule.

3 treatment administration

The treatment involves a single ascending dose of DB-OTO administered through an intracochlear injection. Initially, the injection is given unilaterally (in one ear).

The pharmaceutical form of DB-OTO is an injection, and the route of administration is intracochlear.

4 monitoring and follow-up

The patient is monitored for any treatment-emergent adverse events, both systemic and local.

Follow-up includes auditory tests such as auditory brainstem response (ABR) and behavioral audiometry to assess changes in hearing thresholds and speech reception.

5 expansion cohort

If the initial treatment is well-tolerated, a bilateral injection (in both ears) may be administered in an expansion cohort.

The objective is to evaluate the safety, tolerability, and efficacy of DB-OTO in improving hearing in children and infants with biallelic OTOF mutations.

6 long-term follow-up

The trial includes a long-term follow-up period to monitor the patient’s progress and any long-term effects of the treatment.

The estimated end date for the trial is April 19, 2031.

Who Can Join the Study?

The patient must have changes in both copies of the OTOF gene that are known to cause or likely to cause hearing loss. The OTOF gene is related to hearing.
The patient must be under 18 years old and fit into the age group for the study when the parent or legal guardian agrees to participate. If the child is old enough, they should also agree to participate.
For infants up to 24 months old:
- No response in a hearing test called ABR when a sound is played at a certain loudness in the ear(s) to be treated.
- There should be signs of ear function called otoacoustic emissions (OAE) in the ear(s) to be treated.
For children older than 24 months but under 18 years old:
- No response in a hearing test called ABR when a sound is played at a certain loudness in the ear(s) to be treated.
- There should be signs of ear function called otoacoustic emissions (OAE) in the ear(s) to be treated, or
- There should be signs of ear function called a cochlear microphonic in the ear(s) to be treated.
At least one parent or legal guardian must agree to have the child vaccinated according to the country’s vaccination schedule for children.
The patient should not have any important abnormal results in lab tests at the start of the study.
The patient’s hearing loss should not change with body temperature.
From the start of the study and for 18 months, female patients who can have children and male patients who can father children must agree to use effective birth control. Female patients must agree not to become pregnant, and male patients must agree not to father a child or donate sperm.
There may be other specific requirements to join the study.

Who Cannot Join the Study?

Patients who do not have congenital hearing loss caused by changes in both copies of the otoferlin gene cannot participate. Congenital hearing loss means hearing loss present from birth, and the otoferlin gene is a specific gene related to hearing.
Patients who are not within the specified age range for the study cannot participate. The study is for children and infants.
Patients who have any other medical conditions that might interfere with the study cannot participate.
Patients who are unable to follow the study procedures or attend the required visits cannot participate.
Patients who have participated in another clinical trial recently may not be eligible to participate.
Patients who have any allergies or reactions to the study medication or its ingredients cannot participate.
Patients who are taking certain medications that might interfere with the study cannot participate.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country	Status
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
Universitaetsklinikum Tuebingen AöR	Tuebingen	Germany

Trial status

Country	Status	Recruitment Start
Germany	Recruiting	12.05.2023
Spain	Recruiting	12.05.2023

Trial locations

Investigated drugs:

DB-OTO is a medication being studied for its potential to help children and infants who have specific genetic mutations affecting their hearing. This trial is looking at how safe and tolerable this medication is when injected directly into the ear. The goal is to see if it can improve hearing in those with these genetic changes.

Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF) – This is a genetic condition that affects hearing from birth due to mutations in the otoferlin gene. The otoferlin gene is crucial for the proper functioning of hair cells in the inner ear, which are responsible for converting sound waves into nerve signals. When both copies of this gene are mutated, it leads to a disruption in this process, resulting in hearing loss. The condition is typically identified in infants and young children, as they may not respond to sounds or may have delayed speech development. The progression of hearing loss can vary, but it is generally stable and does not worsen over time.

Trial ID:

2024-511342-40-00

Protocol code:

DB-OTO-001

NCT ID:

NCT05788536

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?