NIPH Clinical Trials Search

A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants with Hearing Loss Due to Otoferlin Mutations

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
Date of first enrollment	01/04/2026
Target sample size	2
Countries of recruitment	USA,Japan,Canada,Japan,Germany,Japan,Spain,Japan,UK,Japan
Study type	Interventional
Intervention(s)	DB-OTO will be administered as a single intracochlear injection into one (Part A) or both ears (Part B). For bilateral injections (Part B), patients will receive DB-OTO in 1 surgical session.

Outcome(s)

Primary Outcome

Incidence and severity of treatment-emergent adverse events Achievement of a hearing sensitivity threshold of <=70 dB assessed by average pure tone audiometry (PTA)

Secondary Outcome

Auditory Brainstem Response (ABR) to click Achievement of a hearing sensitivity threshold of <=45 dB assessed by average PTA Achievement of hearing sensitivity threshold of <=25 dB assessed by average PTA Speech perception scores by age-appropriate tests Speech Awareness Threshold (SAT): achievement of a threshold of <=70 dB SAT: achievement of a threshold of <=45 dB SAT: achievement of threshold of <=25 dB Speech Reception Threshold (SRT): achievement of a threshold of <=70 dB SRT: achievement of a threshold of <=45 dB SRT: achievement of a threshold of <=25 dB Severity in speech perception ability assessed by Global Impression scales, determined by clinician Severity in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian Change in speech perception ability assessed by Global Impression scales, determined by clinician Change in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian Average PTA threshold in the subset of patients who achieved an average PTA threshold <=70 dB Average PTA threshold in the subset of patients who achieved an average PTA threshold >70 dB but <=85 dB Achievement of a hearing sensitivity threshold improvement of >=10 dB from baseline Time to an average PTA threshold <=70 dB Incidence of patients who regress to >70 dB after having achieved average PTA threshold <=70 dB Persistence of an average PTA threshold <=70 dB

Key inclusion & exclusion criteria

Age minimum	Not applicable
Age maximum	< 18age old
Gender	Both
Include criteria	1. Willingness of at least 1 parent/legal guardian to provide written informed consent (and patient to provide assent, when applicable) and willingness to comply with trial protocol; to consent to genetic testing for the patient (and patient to provide assent, when applicable) in order to evaluate a panel of hearing loss-related genes; and to consent to vaccinations for the patient (and patient to provide assent, when applicable) in accordance with the country-specific pediatric immunization schedule as described in the protocol 2. Patient is aged <18 years and able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the parent/legal guardian signing the informed consent form (and patient providing assent, when applicable) 3. Presence of biallelic, likely pathogenic or pathogenic OTOF variants 4. No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol 5. Audiological Criteria: a. Investigator diagnoses the patient with profound sensorineural hearing loss (SNHL; >=90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function b. Outer hair cell presence is confirmed via presence of otoacoustic emissions (>=6 dBSNR) at >=3 frequencies from 1 to 8 kHz in the ear(s) to be injected with DB-OTO. Alternatively, for children >24 months to <18 years of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be injected with DB-OTO. 6. No evidence from measures of hearing loss that show a dependence on body temperature 7. From study the period following informed consent and for the duration of the short-term follow-up period (48 weeks) and in cases of early withdrawal, at least 12 months after DB-OTO administration. Female patients of childbearing potential and fertile males, must agree to use highly effective contraception, as described in the protocol. Female patients must agree not to become pregnant. Fertile male patients must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration.
Exclude criteria	1. Presence of any disease or disorder that, in the opinion of the Investigator, would interfere with conducting the trial, as described in the protocol. 2.History of prior treatment with gene therapy 3. Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI]) in the ear(s) to be injected with DB-OTO 4. History or presence of other permanent or untreatable hearing loss conditions 5. Prior or current history of malignancies 6. Prior or current history of meningitis 7. History or presence of cochlear implants in the ear(s) to be injected with DB-OTO 8. History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, neonatal intensive care unit (NICU) admission, and/or low Apgar scores as described in the protocol