A Study of DB-OTO, an Adeno-associated Virus (AAV) Based Gene Therapy, in Children/Infants With Hearing Loss Due to Otoferlin Mutations (CHORD)
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| ClinicalTrials.gov Identifier: NCT05788536 |
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Recruitment Status :
Recruiting
First Posted : March 29, 2023
Last Update Posted : April 19, 2024
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Sponsor:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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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 |
| 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 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: DB-OTO - Dose Escalation
Unilateral intracochlear dosing
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Genetic: DB-OTO
DB-OTO will be administered as a single intracochlear injection into one ear (Part A).
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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).
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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 :
- Incidence and severity of treatment-emergent systemic and local adverse events [ Time Frame: 5 years ]
Secondary Outcome Measures :
- Auditory brainstem response (ABR) - change in intensity threshold (decibels Hearing Level [dB nHL]) across frequency domains [ Time Frame: 5 years ]
- 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 ]
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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:
- Presence of pathogenic or likely pathogenic mutations in both alleles of the OTOF gene.
- 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
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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:
- Profound sensorineural hearing loss (SNHL; ≥ 90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function.
- 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:
- Profound SNHL (≥ 90 dB HL) based on physiologic measurements (ABR) of inner ear function AND
- Behavioral open-set word recognition scores of < 30% in the ear that would receive DB-OTO
- Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
- Presence of a cochlear microphonic in ears to receive DB-OTO.
UK & Spain:
Infants ≤24 months of age:
- 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.
- Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO.
Children >24 months to <18 years of age:
- 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.
- Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR
- Presence of a cochlear microphonic in ears to receive DB-OTO.
- Willingness of at least 1 parent/legal guardian to consent to vaccinations for the patient in accordance with the country-specific pediatric immunization schedule
- No clinically significant laboratory findings on clinical laboratory tests at time of Screening
- No evidence that hearing loss is dependent on body temperature
- 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:
- History or presence of other permanent or untreatable hearing loss conditions.
- Prior or current cochlear implants in the ear(s) to be injected with DB-OTO
- 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.
- Prior or current history of malignancies.
- Prior or current history of meningitis.
- History of prior treatment with gene therapy.
- 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
| Contact: Clinical Trials Administrator | 844-734-6643 | clinicaltrials@regeneron.com |
Locations
| 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: Sarah Mleziva smleziva@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
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
Additional Information:
| 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: | April 19, 2024 |
| Last Verified: | April 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/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Regeneron Pharmaceuticals:
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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 |