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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05788536
Recruitment Status : Recruiting
First Posted : March 29, 2023
Last Update Posted : June 21, 2024
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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)

Condition or disease Intervention/treatment Phase
Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF) Genetic: DB-OTO Phase 1 Phase 2

Detailed Description:
Former Sponsor Decibel Therapeutics

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: DB-OTO will be administered as a single intracochlear injection into one (Part A) or both ears (Part B). For bilateral injections (Part B), patients will receive DB-OTO in 1 surgical session.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 12, 2023
Estimated Primary Completion Date : April 19, 2031
Estimated Study Completion Date : April 19, 2031


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)

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 both ears (Part B). For bilateral injections (Part B), patients will receive DB-OTO in 1 surgical session.




Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent systemic and local adverse events [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Auditory brainstem response (ABR) - change in intensity threshold (decibels Hearing Level [dB nHL]) across frequency domains [ Time Frame: 5 years ]
  2. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05788536


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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United States, California
UCLA Health- Department of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Akira Ishiyama, MD       aishiyama@mednet.ucla.edu   
United States, Florida
The Nemours Foundation d/b/a Nemours Children's Health Recruiting
Jacksonville, Florida, United States, 32207
Contact: Evie Landry, MD       Evie.Landry@nemours.org   
United States, New York
New York Presbyterian Hospital-Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Lawrence R. Lustig, MD       lrl2125@cumc.columbia.edu   
United States, Ohio
Children's Hospital Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: John Greinwald, MD       john.greinwald@cchmc.org   
United States, Washington
Seattle Children's Hospital dba Seattle Children's Research Institute Recruiting
Seattle, Washington, United States, 98105
Contact: Jay T. Rubinstein, M.D., Ph.D       rubinj@uw.edu   
United States, Wisconsin
The Medical College of Wisconsin, Inc. Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Caroline Rupcich       crupcich@mcw.edu   
Spain
Hospital Universitario Insular Materno-Infantil de Las Palmas Recruiting
Las Palmas de Gran Canaria, Spain, 35016
Contact: Angel Ramos Macias, MD, PhD       ramosorl@idecnet.com   
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Ruben Polo López       rubenpolo1979@gmail.com   
Clinica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Contact: Manuel Jesus Manrique Rodriguez       mmanrique@unav.es   
United Kingdom
Cambridge University Hospitals NHS Foundation Trust Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Manohar Bance, FRCSC       mlb59@cam.ac.uk   
Great Ormond Street Hospital for Children- NHS Foundation Trust Recruiting
London, United Kingdom, WC1N 3JH
Contact: Robert Nash, FRCS       r.nash@ucl.ac.uk   
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
Additional Information:
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05788536    
Other Study ID Numbers: DB-OTO-001
2022-000079-38 ( EudraCT Number )
First Posted: March 29, 2023    Key Record Dates
Last Update Posted: June 21, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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.
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
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
DB-OTO
Gene Therapy
Congenital Hearing Loss
Sensorineural Hearing Loss
Auditory Neuropathy
Pediatric
Cochlear Implant
Otoferlin
Deaf
Hard of hearing
Hearing impaired
Hearing disorder
Fully implantable hearing aid
Child
Infant
CHORD
Additional relevant MeSH terms:
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Hearing Loss
Deafness
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases