Gene therapy for children with hearing loss from otoferlin mutations

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study evaluates DB-OTO, a gene therapy designed to treat congenital hearing loss caused by mutations in the otoferlin gene. It aims to assess the safety and tolerability of DB-OTO in children and infants, as well as its efficacy in improving hearing. Participants must have specific genetic mutations and meet certain audiological criteria to qualify for the study. The trial is being conducted at multiple locations, including medical centers in California and Florida.

Why it matters

Who can join: the full rules

Key Inclusion Criteria:

1. Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
2. Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
3. Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
4. Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
5. Presence of biallelic, likely pathogenic or pathogenic OTOF variants
6. No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
7. Audiological Criteria:

   1. Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
   2. 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 infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
8. No evidence from measures of hearing loss that show a dependence on body temperature
9. From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants 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.

Key Exclusion Criteria:

1. History of prior treatment with gene therapy
2. 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 infused with DB-OTO
3. History or presence of other permanent or untreatable hearing loss conditions
4. Prior or current history of malignancies
5. Prior or current history of meningitis
6. History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
7. 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

Note: Other protocol-defined inclusion/exclusion criteria apply

Where it's running

• University of California Los Angeles Medical Center
  Los Angeles, California, United States Recruiting
• Rady Children's Hospital
  San Diego, California, United States Recruiting
• Nemours Children s Clinic
  Jacksonville, Florida, United States Recruiting
• Nemours Childrens Hospital
  Orlando, Florida, United States Recruiting
• Boston Children's Hospital - Main
  Boston, Massachusetts, United States Recruiting
• Columbia University Irving Medical Center
  New York, New York, United States Recruiting

Study contacts

• Study coordinator: Clinical Trials Administrator
• Email: clinicaltrials@regeneron.com
• Phone: 844-734-6643

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.