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A Study of DB-OTO, an 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 : February 7, 2024
Sponsor:
Information provided by (Responsible Party):
Decibel Therapeutics

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

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

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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 : August 19, 2030
Estimated Study Completion Date : August 19, 2030


Arm Intervention/treatment
Experimental: DB-OTO - Dose Escalation
Unilateral intracochlear dosing
Biological: 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).
Biological: 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 may 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: Decibel Therapeutics, Inc. +1-617-370-8701 clinicaltrials@decibeltx.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, 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   
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
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
Decibel Therapeutics
Additional Information:
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Responsible Party: Decibel Therapeutics
ClinicalTrials.gov Identifier: NCT05788536    
Other Study ID Numbers: DB-OTO-001
First Posted: March 29, 2023    Key Record Dates
Last Update Posted: February 7, 2024
Last Verified: February 2024

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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 Decibel Therapeutics:
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