A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants, Adolescents and Adults With Hearing Loss Due to Otoferlin Mutations (CHORD)

August 4, 2026 updated by: Regeneron Pharmaceuticals

A Phase 1/2, Open-Label, Multicenter Trial With a Single Ascending Dose Cohort With Unilateral Intracochlear Injection Followed by a Bilateral Injection Expansion Cohort to Evaluate the Safety, Tolerability, and Efficacy of DB-OTO in Children and Infants With Biallelic hOTOF Mutations

Regeneron is conducting a study of an investigational new drug called DB-OTO. DB-OTO is a gene therapy that is being developed to treat pediatric and adult participants who have severe-to profound and profound hearing loss due to changes in the otoferlin gene.

The purpose of this study is to:

  • Learn about the safety of DB-OTO
  • Determine how well DB-OTO is tolerated (does not cause ongoing discomfort)
  • Evaluate the efficacy of DB-OTO (how well DB-OTO works)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Former Sponsor Decibel Therapeutics

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Germany
  • Japan
    • Nagano
      • Matsumoto-shi, Nagano, Japan, 390-8621
  • Spain
      • Barcelona, Spain, 08950
      • Las Palmas de Gran Canaria, Spain, 35016
        • Withdrawn
        • Hospital Universitario Materno Infantil en las Palmas de Gran Canaria
      • Madrid, Spain, 28034
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra- Pamplona
        • Contact:
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrooke's Hospital, Cambridge University Hospitals NHS FT
        • Contact:
      • London, United Kingdom, WC1N 3JH
        • Recruiting
        • Great Ormond street Hospital for Children NHS Foundation Trust
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90024
        • Recruiting
        • University of California Los Angeles Medical Center
        • Contact:
      • San Diego, California, United States, 92123
    • Florida
      • Jacksonville, Florida, United States, 32207
      • Orlando, Florida, United States, 32827
    • Massachusetts
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DB-OTO - Part A
Unilateral intracochlear dosing
Genetic: DB-OTO
Administered per the protocol
Other Names:
  • Otarmeni™
  • Otoferlin
Experimental: DB-OTO - Part B
Bilateral intracochlear dosing using the dose selected based on safety and efficacy data from Part A
Genetic: DB-OTO
Administered per the protocol
Other Names:
  • Otarmeni™
  • Otoferlin
Experimental: DB-OTO - Part C
Unilateral or bilateral intracochlear dosing
Genetic: DB-OTO
Administered per the protocol
Other Names:
  • Otarmeni™
  • Otoferlin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Up to week 104
Up to week 104
Achievement of a hearing sensitivity threshold of ≤70 dB assessed by average Pure Tone Audiometry (PTA)
Time Frame: Up to week 104
Up to week 104

Secondary Outcome Measures

Outcome Measure
Time Frame
Speech Awareness Threshold (SAT): achievement of a threshold of ≤70 dB
Time Frame: Up to week 48
Up to week 48
SAT: achievement of a threshold of ≤45 dB
Time Frame: Up to week 48
Up to week 48
SAT: achievement of threshold of ≤25 dB
Time Frame: Up to week 48
Up to week 48
Achievement of a hearing sensitivity threshold improvement of ≥10 dB from baseline
Time Frame: Up to week 48
Up to week 48
Achievement of a score ≥3 on the Early Speech Perception (ESP) test
Time Frame: At week 104
At week 104
Achievement of hearing sensitivity threshold of ≤45 dB assessed by average PTA
Time Frame: Up to week 104
Up to week 104
Achievement of hearing sensitivity threshold of ≤25 dB assessed by average PTA
Time Frame: Up to week 104
Up to week 104
Achievement of a score of 4 on the ESP test
Time Frame: At week 104
At week 104
Time to an average PTA threshold ≤70 dB
Time Frame: Up to week 104
Up to week 104
Persistence of an average PTA threshold ≤70 dB
Time Frame: Up to week 104
Up to week 104
Severity in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)
Time Frame: At week 104
At week 104
Change in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)
Time Frame: At week 104
At week 104
Change from baseline on LittlEARS®
Time Frame: At week 104
At week 104
Change in scores on LittlEARS®
Time Frame: At week 104
At week 104
Change from baseline on Auditory Skills Checklist
Time Frame: At week 104
At week 104
Change in scores on Auditory Skills Checklist
Time Frame: At week 104
At week 104
Clinical assessments of speech production: articulation
Time Frame: At week 104
At week 104
Clinical assessments of speech production: speech intelligibility
Time Frame: At week 104
At week 104
Auditory Brainstem Response (ABR) to click stimulus at ≤90 dB normalized Hearing Level (nHL)
Time Frame: Up to week 48
Up to week 48
Speech perception scores by age-appropriate tests
Time Frame: Up to week 104
Up to week 104
Average PTA threshold in the subset of participants who achieved an average PTA threshold ≤70 dB
Time Frame: Up to week 104
Up to week 104
Average PTA threshold in the subset of participants who achieved an average PTA threshold >70 dB but ≤85 dB
Time Frame: Up to week 48
Up to week 48
Achievement of a hearing sensitivity threshold improvement of ≤85 dB HL, as assessed by PTA
Time Frame: Up to week 48
Up to week 48
Incidence of participants who regress to >70 dB after having achieved average PTA threshold
Time Frame: Up to week 104
Up to week 104
Presence of ABR to click at ≤90 dB nHL
Time Frame: At week 104
At week 104
Change from baseline on MacArthur-Bates Communicative Development Inventories (MB-CDI)
Time Frame: At week 104
At week 104
Change in scores on MB-CDI
Time Frame: At week 104
At week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2023

Primary Completion (Estimated)

February 26, 2029

Study Completion (Estimated)

February 25, 2032

Study Registration Dates

First Submitted

March 15, 2023

First Submitted That Met QC Criteria

March 15, 2023

First Posted (Actual)

March 29, 2023

Study Record Updates

Last Update Posted (Actual)

August 5, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DB-OTO-001
  • 2022-000079-38 (EudraCT Number)
  • 2024-511342-40-00 (Ctis: EUCT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

  • received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
  • made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
  • the legal authority to share the data, and
  • ensured the ability to protect participant privacy.

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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