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

Withdrawn

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

• Registration Number: NCT06019481
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

Former Sponsor Decibel Therapeutics

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.

Study Timeline

• Study First Submitted: 2023-08-21
• Study First Submitted QC: 2023-08-25
• Study First Posted: 2023-08-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Study Start: 2025-06-30
• Primary Completion: 2030-06-30
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Hearing-related outcomes	4 years	Speech detection and perception thresholds.

Secondary Outcome Measures

Name	Time	Method
Auditory skills and speech perception over time	4 years	Auditory Skills Checklist (ASC)

Trial Locations

Locations (2)

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States