Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
Conditions
Interventions
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.
Sponsors
Inomata Hyoe
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 =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.
Exclusion criteria
Exclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Auditory Brainstem Response (ABR) to click Achievement of a hearing sensitivity threshold of 70 dB but =10 dB from baseline Time to an average PTA threshold 70 dB after having achieved average PTA threshold <=70 dB Persistence of an average PTA threshold <=70 dB | — |
Countries
Canada, Germany, Japan, Spain, UK, USA
Contacts
Public ContactRegeneron Japan Contact for Clinical Trial
Regeneron Japan KK
Outcome results
None listed