Open Actively Recruiting

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

About

Brief Summary

This is a first-in-human, multicenter, Phase 1/2, open-label, 2-part trial with a single-ascending dose patient cohort (Part A) and a bilateral expansion patient cohort (Part B) to evaluate the safety, tolerability, and preliminary efficacy of DB-OTO, an AAV based gene therapy in pediatric patients with biallelic OTOF mutations

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I/II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
N/A
Maximum Age
17 Years

Inclusion Criteria:

  • Presence of pathogenic or likely pathogenic mutations in both alleles of the OTOF gene.
  • Patient is <18 years of age and of the appropriate age to qualify for enrollment in the corresponding age cohort at the time the parent/legal guardian signs the informed consent form. Participant to provide assent, when applicable
  • Audiological Criteria: US:
    • Investigator determines that minimal benefit has been provided by amplification of the ear to receive DB-OTO.
    • Investigator determines the patient meets cochlear implantation criteria in both ears according to the recommended cochlear implant label Infants ≤24 months of age:
    • Profound sensorineural hearing loss (SNHL; ≥ 90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function.
    • Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO Children >24 months to <18 years of age:
    • Profound SNHL (≥ 90 dB HL) based on physiologic measurements (ABR) of inner ear function AND
    • Behavioral open-set word recognition scores of < 30% in the ear that would receive DB-OTO
    • Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
    • Presence of a cochlear microphonic in ears to receive DB-OTO. UK & Spain: Infants ≤24 months of age:
    • Absence of an ABR neural signal in response to a click stimulus ≤85 dB nHL in the ear(s) to be injected with DB-OTO.
    • Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO. Children >24 months to <18 years of age:
    • Absence of an ABR neural signal in response to a click stimulus ≤85 dB nHL in the ear(s) to be injected with DB-OTO.
    • Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
    • Presence of a cochlear microphonic in ears to receive DB-OTO.
  • Willingness of at least 1 parent/legal guardian to consent to vaccinations for the patient in accordance with the country-specific pediatric immunization schedule
  • No clinically significant laboratory findings on clinical laboratory tests at time of Screening
  • No evidence that hearing loss is dependent on body temperature
  • From study start and for the duration of the short-term follow-up period (18 months): Female patients of childbearing potential and fertile males, must agree to use highly effective contraception. Female patients must agree not to become pregnant. Fertile male patients must agree not to father a child or donate sperm.

Exclusion Criteria:

  • History or presence of other permanent or untreatable hearing loss conditions.
  • Prior or current cochlear implants in the ear(s) to be injected with DB-OTO
  • History of risk factor(s) for auditory neuropathy not caused by OTOF mutations including: prematurity, low birth weight, hyperbilirubinemia, neonatal intensive care unit (NICU) admission, and/or low Apgar scores.
  • Prior or current history of malignancies.
  • Prior or current history of meningitis.
  • History of prior treatment with gene therapy.
  • Surgical anatomy that would preclude 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.

Note: additional inclusion/exclusion criteria may apply, per protocol.

Join this Trial

Contact our clinical trial navigators for opportunities that may be suitable for you
Share:
Study Stats
Protocol No.
22-5129
Category
Genetic and Rare Diseases
Pediatric and Prenatal Disorders
Contact
Adreanne Rivera
Location
  • UCLA Westwood
For Providers
NCT No.
NCT05788536
For detailed technical eligibility, visit ClinicalTrials.gov.