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

April 17, 2024 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 children who have 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)

22

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

  • Spain
      • Las Palmas de Gran Canaria, Spain, 35016
        • Recruiting
        • Hospital Universitario Insular Materno-Infantil de Las Palmas
        • Contact:
      • Madrid, Spain, 28034
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Cambridge University Hospitals NHS Foundation Trust
        • 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, 90095
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Recruiting
        • The Nemours Foundation d/b/a Nemours Children's Health
        • Contact:
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • New York Presbyterian Hospital-Columbia University Medical Center
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital dba Seattle Children's Research Institute
        • Contact:
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • The Medical College of Wisconsin, Inc.
        • 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)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Presence of pathogenic or likely pathogenic mutations in both alleles of the OTOF gene.
  2. 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

  3. 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:

    1. Profound sensorineural hearing loss (SNHL; ≥ 90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function.
    2. 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:

    1. Profound SNHL (≥ 90 dB HL) based on physiologic measurements (ABR) of inner ear function AND
    2. Behavioral open-set word recognition scores of < 30% in the ear that would receive DB-OTO
    3. Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
    4. Presence of a cochlear microphonic in ears to receive DB-OTO.

    UK & Spain:

    Infants ≤24 months of age:

    1. 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.
    2. Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO.

    Children >24 months to <18 years of age:

    1. 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.
    2. Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
    3. Presence of a cochlear microphonic in ears to receive DB-OTO.
  4. Willingness of at least 1 parent/legal guardian to consent to vaccinations for the patient in accordance with the country-specific pediatric immunization schedule
  5. No clinically significant laboratory findings on clinical laboratory tests at time of Screening
  6. No evidence that hearing loss is dependent on body temperature
  7. 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:

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

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 - Dose Escalation
Unilateral intracochlear dosing
Genetic: DB-OTO

DB-OTO will be administered as a single intracochlear injection into one ear (Part A).

  • LD Cohort (starting dose)
  • HD Cohort (high dose)
Genetic: DB-OTO
DB-OTO will be administered as a single intracochlear injection into both ears (Part B). For bilateral injections (Part B), patients will receive DB-OTO in 1 surgical session.
Experimental: DB-OTO - Dose Expansion
Bilateral intracochlear dosing using the dose selected based on safety and efficacy data from the Dose Escalation phase (Part A).
Genetic: DB-OTO

DB-OTO will be administered as a single intracochlear injection into one ear (Part A).

  • LD Cohort (starting dose)
  • HD Cohort (high dose)
Genetic: DB-OTO
DB-OTO will be administered as a single intracochlear injection into both ears (Part B). For bilateral injections (Part B), patients will receive DB-OTO in 1 surgical session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of treatment-emergent systemic and local adverse events
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Auditory brainstem response (ABR) - change in intensity threshold (decibels Hearing Level [dB nHL]) across frequency domains
Time Frame: 5 years
5 years
Behavioral audiometry with pure-tone audiometry - change in intensity thresholds (dB HL) in treated ear across frequency domains, and speech awareness threshold (SAT) and speech reception threshold (SRT)- change in threshold in treated ear
Time Frame: 5 years
5 years

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.

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)

May 12, 2023

Primary Completion (Estimated)

April 19, 2031

Study Completion (Estimated)

April 19, 2031

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)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DB-OTO-001
  • 2022-000079-38 (EudraCT Number)

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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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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