A Natural History Study in Pediatric Participants With Hearing Loss Due to OTOF, GJB2, or GJB2/GJB6 Mutations

Study Overview
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Brief Summary
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This is an observational study to examine the characteristics of gene-related hearing loss in pediatric participants with biallelic otoferlin (OTOF) Mutations, Gap Junction Beta 2 (GJB2) Mutations, or Digenic GJB2/Gap Junction Beta 6 (GJB6) Mutations. This study will follow the participant for 4 years with annual visits each year.

Detailed Description
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This is a longitudinal, retrospective and prospective, low interventional study designed to collect data on the natural history of pediatric participants with OTOF, GJB2, or GJB2/GJB6 gene mutations to assess hearing-related outcomes, auditory skills, and speech perception. No investigational product will be administered. At study visits, participants will undergo physiological and behavioral assessments of hearing and vestibular function. Additionally, parents/legal guardians or participants will complete questionnaires that will include the capture of epidemiologic, quality-of-life, auditory and language development, and health resource utilization information.

Official Title
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A Retrospective and Prospective Natural History Study to Examine the Characteristics of Gene-Related Hearing Loss in Pediatric Participants With Biallelic Otoferlin (OTOF) Mutations, Gap Junction Beta 2 (GJB2) Mutations, Or Digenic GJB2/Gap Junction Beta 6 (GJB6) Mutations

Conditions
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Congenital Hearing Loss Secondary to Biallelic Mutations in the Otoferlin Gene (OTOF), Biallelic Mutations in the Gap Junction Beta 2 (GJB2) Gene, Digenic Mutations in GJB2/Gap Junction Beta 6 (GJB6) Genes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is no older than 7 years (inclusive) at the time of the parent/legal guardian signing the informed consent form (ICF) Participant has 1 of the following genotypes and meets the associated audiologic criteria based on physiologic and/or behavioral measures of inner ear function: Biallelic pathogenic or likely pathogenic OTOF mutations with severe to profound sensorineural hearing loss (SNHL; ≥ 85 dB HL) and confirmed presence of OAEs Biallelic pathogenic and truncating GJB2 mutation(s) with moderate or moderately-severe SNHL (≤41 to <71 dB HL) Digenic pathogenic or likely pathogenic mutations in GJB2 and GJB6 genes with mild or worse SNHL (>26 dB HL) Participant has at least 1 ear that has not received a cochlear implant (CI) Exclusion Criteria: History of or active participation in an interventional trial related to hearing loss History or presence of any other permanent/untreatable hearing loss conditions, including genetic conditions other than those involving biallelic OTOF or GJB2 mutations, or digenic GJB2/GJB6 mutations History of treatment with ototoxic drugs

Ages Eligible for Study
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Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hearing-related outcomes | Auditory brainstem response (ABR) intensity | 4 years | 
| Hearing-related outcomes | Otoacoustic emission (OAEs) amplitudes | 4 years | 
| Hearing-related outcomes | Pure tone intensity thresholds | 4 years | 
| Hearing-related outcomes | Speech detection and perception thresholds. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Auditory skills and speech perception over time | Open- and Closed- set Task phoneme accuracy and word comprehension | 4 years | 
| Auditory skills and speech perception over time | Early Speech Perception (ESP) | 4 years | 
| Auditory skills and speech perception over time | Pediatric Speech Intelligibility (PSI) test | 4 years | 
| Auditory skills and speech perception over time | Auditory Skills Checklist (ASC) | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital Hearing Loss, Sensorineural Hearing Loss, Auditory Neuropathy, Pediatric, Cochlear Implant, Otoferlin, GJB2, GJB6, OTOF, Deaf, Hard of hearing, Hearing impaired, Hearing disorder, Fully implantable hearing aid, Child, Infant, ENSEMBLE, Gap Junction Beta 6 Genes, Gap Junction Beta 2 Genes