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

Phase 1

Recruiting

• Conditions: Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)

• Registration Number: NCT05788536
• Lead Sponsor: 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)

Detailed Description

Former Sponsor Decibel Therapeutics

Study Timeline

• Study First Submitted: 2023-03-15
• Study First Submitted QC: 2023-03-15
• Study First Posted: 2023-03-29
• Study Start: 2023-06-27
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-11
• Primary Completion: 2031-04-19
• Study Completion: 2031-04-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Willingness of at least 1 parent/legal guardian to provide written informed consent (and patient to provide assent, when applicable) and willingness to comply with trial protocol; to consent to genetic testing for the patient (and patient to provide assent, when applicable) in order to evaluate a panel of hearing loss-related genes; and to consent to vaccinations for the patient (and patient to provide assent, when applicable) in accordance with the country-specific pediatric immunization schedule as described in the protocol

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.

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 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

Note: Other protocol-defined inclusion/exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment-emergent adverse events	Up to week 48
Achievement of a hearing sensitivity threshold of ≤70 dB assessed by average pure tone audiometry (PTA)	Up to week 48

Secondary Outcome Measures

Name	Time	Method
Auditory Brainstem Response (ABR) to click	Up to week 48
Achievement of hearing sensitivity threshold of ≤25 dB assessed by average PTA	Up to week 48
Speech Awareness Threshold (SAT): achievement of a threshold of ≤70 dB	Up to week 48
SAT: achievement of a threshold of ≤45 dB	Up to week 48
SAT: achievement of threshold of ≤25 dB	Up to week 48
Achievement of a hearing sensitivity threshold of ≤45 dB assessed by average PTA	Up to week 48
Speech Reception Threshold (SRT): achievement of a threshold of ≤70 dB	Up to week 48
SRT: achievement of a threshold of ≤45 dB	Up to week 48
SRT: achievement of a threshold of ≤25 dB	Up to week 48
Severity in speech perception ability assessed by Global Impression scales, determined by clinician	Up to week 48
Severity in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian	Up to week 48
Change in speech perception ability assessed by Global Impression scales, determined by clinician	Up to week 48
Change in speech perception ability assessed by Global Impression scales, determined by parent/legal guardian	Up to week 48
Average PTA threshold in the subset of patients who achieved an average PTA threshold ≤70 dB	Up to week 48
Average PTA threshold in the subset of patients who achieved an average PTA threshold >70 dB but ≤85 dB	Up to week 48
Speech perception scores by age-appropriate tests	Up to week 48
Achievement of a hearing sensitivity threshold improvement of ≥10 dB from baseline	Up to week 48
Time to an average PTA threshold ≤70 dB	Up to week 48
Incidence of patients who regress to >70 dB after having achieved average PTA threshold ≤70 dB	Up to week 48
Persistence of an average PTA threshold ≤70 dB	Up to week 48

Trial Locations

Locations (15)

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Boston Children's Hospital - Main; 🇺🇸 Boston, Massachusetts, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

University Hospital Tubingen; 🇩🇪 Tubingen, Germany

Clinica Universidad de Navarra- Pamplona; 🇪🇸 Pamplona, Spain

University of California Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

Nemours Children s Clinic; 🇺🇸 Jacksonville, Florida, United States

Nemours Childrens Hospital; 🇺🇸 Orlando, Florida, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

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