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

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

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.

Study Overview

• Status: Recruiting
• Conditions: 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

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 Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
      • Contact: Mark E. Gerber, MD; Phone Number: 602-933-4134; Email: mgerber1@phoenixchildrens.com
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Ursula Findlen, Ph.D.; Phone Number: 614-722-6526; Email: Ursula.Findlen@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric participants no older than 7 years, inclusive, who have genetic hearing loss due to OTOF, GJB2, or GJB2/GJB6 mutations.

Description

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 Plan

How is the study designed?

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life over time	Quality of Life-Cochlear Implant (QoL-CI) score	4 years
Quality of life over time	Pediatric Quality of Life (PedsQL) Generic Core Scales dimension and total score	4 years
Quality of life over time	Hearing Environments and Reflection on Quality of Life (HEAR-QL-26) subscale and overall score	4 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Patients, Caregivers & Healthcare Providers: Contribute to Genetic Hearing Loss Research

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): August 31, 2023

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Child; Pediatric; Infant; Cochlear Implant; Deaf; Sensorineural Hearing Loss; Congenital Hearing Loss; Auditory Neuropathy; Otoferlin; Hard of hearing; Hearing impaired; Hearing disorder; Fully implantable hearing aid; GJB2; GJB6; OTOF; ENSEMBLE; Gap Junction Beta 6 Genes; Gap Junction Beta 2 Genes
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: DB-100-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No