RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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)

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

Quick Facts

Study Start:2023-05-12

Study Completion:2031-04-19

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05788536

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 17 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion 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: * 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 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 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. 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. 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.	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.

Inclusion Criteria

Exclusion 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:
* 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
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
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.
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.
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.

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.

Contacts and Locations

Study Contact

Clinical Trials Administrator

CONTACT

844-734-6643

clinicaltrials@regeneron.com

Principal Investigator

Clinical Trial Management

STUDY_DIRECTOR

Regeneron Pharmaceuticals

Study Locations (Sites)

UCLA Health- Department of Medicine

Los Angeles, California, 90095

United States

The Nemours Foundation d/b/a Nemours Children's Health

Jacksonville, Florida, 32207

United States

The Nemours Foundation d/b/a Nemours Children's Health

Orlando, Florida, 32827

United States

New York Presbyterian Hospital-Columbia University Medical Center

New York, New York, 10032

United States

Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

Seattle Children's Hospital dba Seattle Children's Research Institute

Seattle, Washington, 98105

United States

The Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Regeneron Pharmaceuticals

Clinical Trial Management, STUDY_DIRECTOR, Regeneron Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-12

Study Completion Date2031-04-19

Study Record Updates

Study Start Date2023-05-12

Study Completion Date2031-04-19

Terms related to this study

Keywords Provided by Researchers

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

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