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

Key Inclusion 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 withtrial protocol; to consent to genetic testing for the patient (and patient toprovide assent, when applicable) in order to evaluate a panel of hearingloss-related genes; and to consent to vaccinations for the patient (and patient toprovide assent, when applicable) in accordance with the country-specific pediatricimmunization schedule as described in the protocol

2. Patient is aged <18 years and able to perform all necessary assessments to qualifyfor enrollment and dosing in the corresponding cohort at the time the parent/legalguardian signing the informed consent form (and patient providing assent, whenapplicable)

3. Presence of biallelic, likely pathogenic or pathogenic OTOF variants

4. No clinically significant laboratory findings on clinical laboratory tests at timeof Screening as described in the protocol

5. Audiological Criteria:

6. Investigator diagnoses the patient with profound sensorineural hearing loss (SNHL; ≥90 dB HL) based on behavioral and physiologic measurements (ABR) ofinner ear function

7. Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be injected withDB-OTO. Alternatively, for children >24 months to <18 years of age, outer haircell presence can be confirmed via presence of the cochlear microphonic in theear(s) to be injected with DB-OTO.

8. No evidence from measures of hearing loss that show a dependence on body temperature

9. From study start and for the duration of the short-term follow-up period (48 weeks):Female patients of childbearing potential and fertile males, must agree to usehighly effective contraception. Female patients must agree not to become pregnant.Fertile male patients must agree not to father a child or donate sperm, for 48 weeksand in cases of early withdrawal, for at least 12 months after DB-OTOadministration.

Key Exclusion Criteria:

1. History of prior treatment with gene therapy

2. Surgical anatomy that would preclude or meaningfully impact the planned surgicalapproach as indicated by medical imaging (eg, computed tomography [CT] or magneticresonance imaging [MRI]) in the ear(s) to be injected with DB-OTO

3. History or presence of other permanent or untreatable hearing loss conditions

4. Prior or current history of malignancies

5. Prior or current history of meningitis

6. History or presence of cochlear implants in the ear(s) to be injected with DB-OTO

7. History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenicvariants including but not limited to: prematurity, low birth weight,hyperbilirubinemia, neonatal intensive care unit (NICU) admission, and/or low Apgarscores as described in the protocol

Note: Other protocol-defined inclusion/exclusion criteria apply