Gene therapy for children with hearing loss from otoferlin mutations
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
This study is testing a new gene therapy called DB-OTO to see if it can help children with hearing loss caused by specific genetic mutations improve their hearing.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | N/A to 17 Years |
| Sex | All |
| Sponsor | Regeneron Pharmaceuticals Industry-sponsored |
| Locations | 16 sites (Los Angeles, California and 15 other locations) |
| Trial ID | NCT05788536 on ClinicalTrials.gov |
What this trial studies
This study evaluates DB-OTO, a gene therapy designed to treat congenital hearing loss caused by mutations in the otoferlin gene. It aims to assess the safety and tolerability of DB-OTO in children and infants, as well as its efficacy in improving hearing. Participants must have specific genetic mutations and meet certain audiological criteria to qualify for the study. The trial is being conducted at multiple locations, including medical centers in California and Florida.
Who should consider this trial
Good fit: Ideal candidates are children and infants under 18 years with pathogenic mutations in both alleles of the OTOF gene and profound sensorineural hearing loss.
Not a fit: Patients with hearing loss not caused by otoferlin mutations or those who do not meet the specific audiological criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could restore hearing in children with specific genetic hearing loss, significantly improving their quality of life.
How similar studies have performed: Other studies using gene therapy for hearing loss have shown promise, indicating potential for success with this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Key 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
Where this trial is running
Los Angeles, California and 15 other locations
- University of California Los Angeles Medical Center — Los Angeles, California, United States (Recruiting)
- Rady Children's Hospital — San Diego, California, United States (Recruiting)
- Nemours Children s Clinic — Jacksonville, Florida, United States (Recruiting)
- Nemours Childrens Hospital — Orlando, Florida, United States (Recruiting)
- Boston Children's Hospital - Main — Boston, Massachusetts, United States (Recruiting)
- Columbia University Irving Medical Center — New York, New York, United States (Recruiting)
- Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (Recruiting)
- Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)
- Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)
- University Hospital Tubingen — Tübingen, Germany (Recruiting)
- Shinshu University Hospital — Matsumoto-shi, Nagano, Japan (Recruiting)
- Clinica Universidad de Navarra- Pamplona — Pamplona, Navarre, Spain (Recruiting)
- Hospital Universitario Materno Infantil en las Palmas de Gran Canaria — Las Palmas de Gran Canaria, Spain (Withdrawn)
- Ramon y Cajal University Hospital — Madrid, Spain (Recruiting)
- Addenbrooke's Hospital, Cambridge University Hospitals NHS FT — Cambridge, United Kingdom (Recruiting)
- Great Ormond Street Hospital For Children NHS Foundation Trust — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Clinical Trials Administrator
- Email: clinicaltrials@regeneron.com
- Phone: 844-734-6643
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.