A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants With Hearing Loss Due to Otoferlin Mutations
NCT ID: NCT05788536
Last Updated: 2025-10-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
30 participants
INTERVENTIONAL
2023-06-27
2031-04-19
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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)
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
An Investigator Initiated Study for OTOV101N+OTOV101C Injection
NCT05901480
A Clinical Trial of EHT102 Injection in Pediatric Patients With Biallelic hOTOF Mutations
NCT07288580
A Natural History Study in Pediatric Participants With Hearing Loss Due to OTOF, GJB2, or GJB2/GJB6 Mutations
NCT06019481
A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06370351
Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
NCT05821959
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
DB-OTO - Unilateral Dose Escalation
Part A: Unilateral intracochlear dosing
DB-OTO
DB-OTO will be administered as a single intracochlear injection into one ear (Part A).
* LD Cohort (lower dose)
* HD Cohort (high dose) - not implemented
DB-OTO - Bilateral Dose Expansion
Part B: Bilateral intracochlear dosing using the dose selected based on safety and efficacy data from Part A.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
DB-OTO
DB-OTO will be administered as a single intracochlear injection into one ear (Part A).
* LD Cohort (lower dose)
* HD Cohort (high dose) - not implemented
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patient is aged \<18 years and able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the parent/legal guardian signing the informed consent form (and patient providing assent, when applicable)
3. Presence of biallelic, likely pathogenic or pathogenic OTOF variants
4. No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
5. Audiological Criteria:
1. Investigator diagnoses the patient 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 injected with DB-OTO. Alternatively, for children \>24 months to \<18 years of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be injected with DB-OTO.
6. No evidence from measures of hearing loss that show a dependence on body temperature
7. From study start and for the duration of the short-term follow-up period (48 weeks): 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, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration.
Exclusion Criteria
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 injected 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 injected 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
17 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Regeneron Pharmaceuticals
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Clinical Trial Management
Role: STUDY_DIRECTOR
Regeneron Pharmaceuticals
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California Los Angeles Medical Center
Los Angeles, California, United States
Rady Children's Hospital
San Diego, California, United States
Nemours Children s Clinic
Jacksonville, Florida, United States
Nemours Childrens Hospital
Orlando, Florida, United States
Boston Children's Hospital - Main
Boston, Massachusetts, United States
Columbia University Irving Medical Center
New York, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Seattle Children's Hospital
Seattle, Washington, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
University Hospital Tubingen
Tübingen, , Germany
Hospital Universitario Materno Infantil en las Palmas de Gran Canaria
Las Palmas de Gran Canaria, , Spain
Ramon y Cajal University Hospital
Madrid, , Spain
Clinica Universidad de Navarra- Pamplona
Pamplona, , Spain
Addenbrooke's Hospital, Cambridge University Hospitals NHS FT
Cambridge, , United Kingdom
Great Ormond Street Hospital For Children NHS Foundation Trust
London, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Valayannopoulos V, Bance M, Carvalho DS, Greinwald JH Jr, Harvey SA, Ishiyama A, Landry EC, Lowenheim H, Lustig LR, Manrique M, Nash R, Polo R, Pritchett CV, Rubinstein JT, Shearer AE, Del Castillo I, Anderson JJ, Corrales CE, Quigley TM, Riggs WJ, Weber P, Wilson G, Irvin SC, Hassan HE, Chen Y, Liu R, Drummond MC, Sabin LR, Musser BJ, Yancopoulos GD, Kyratsous CA, Herman GA, Baras A, Whitton JP; CHORD Study Group. DB-OTO Gene Therapy for Inherited Deafness. N Engl J Med. 2025 Oct 12. doi: 10.1056/NEJMoa2400521. Online ahead of print.
Related Links
Access external resources that provide additional context or updates about the study.
Patients, Caregivers \& HCPs: Contribute to Genetic Hearing Loss Research
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2022-000079-38
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2024-511342-40-00
Identifier Type: CTIS
Identifier Source: secondary_id
DB-OTO-001
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.