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

Inclusion Criteria: Presence of pathogenic or likely pathogenic mutations in both alleles of the OTOF gene. Patient is of the appropriate age to qualify for enrollment in the corresponding age cohort at the time the parent/legal guardian signs the informed consent form For US and UK - Age of the patient - (infants to < 18 years of age at the time of the parent/legal guardian signing the informed consent form). Participant to provide assent, when applicable For Spain - 24 months of age or younger at the time of the parent/legal guardian signing the informed consent form Audiological Criteria: US: Investigator determines that minimal benefit has been provided by amplification of the ear to receive DB-OTO. Investigator determines the patient meets cochlear implantation criteria in both ears according to the recommended cochlear implant label Infants ≤24 months of age: Profound sensorineural hearing loss (SNHL; ≥ 90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function. Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO Children >24 months to <18 years of age: Profound SNHL (≥ 90 dB HL) based on physiologic measurements (ABR) of inner ear function AND Behavioral open-set word recognition scores of < 30% in the ear that would receive DB-OTO Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR Presence of a cochlear microphonic in ears to receive DB-OTO. UK & Spain: Absence of an ABR neural signal in response to a click stimulus ≤85 dB nHL in the ear(s) to be injected with DB-OTO. Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO Willingness of at least 1 parent/legal guardian to consent to vaccinations for the patient in accordance with the country-specific pediatric immunization schedule No clinically significant laboratory findings on clinical laboratory tests at time of Screening No evidence that hearing loss is dependent on body temperature (For US and UK only) - From study start and for the duration of the short-term follow-up period (18 months): Female patients of childbearing potential and fertile males, must agree to use highly effective contraception Female patients must agree not to become pregnant. Fertile male patients must agree not to father a child or donate sperm. Exclusion Criteria: History or presence of other permanent or untreatable hearing loss conditions. Prior or current cochlear implants in the ear(s) to be injected with DB-OTO History of risk factor(s) for auditory neuropathy not caused by OTOF mutations including: prematurity, low birth weight, hyperbilirubinemia, neonatal intensive care unit (NICU) admission, and/or low Apgar scores. Prior or current history of malignancies. Prior or current history of meningitis. History of prior treatment with gene therapy. Surgical anatomy that would preclude 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. Note: additional inclusion/exclusion criteria may apply, per protocol.