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

Phase 2RecruitingNCT05788536

Regeneron Pharmaceuticals30 enrolled

Overview

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)

Former Sponsor Decibel Therapeutics

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

Eligibility

Sex: ALLMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (16)

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

...and 6 more locations

Outcomes

Primary Outcomes

Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)

Time frame: Up to week 104

Achievement of a hearing sensitivity threshold of ≤70 dB assessed by average Pure Tone Audiometry (PTA)

Time frame: Up to week 104

Secondary Outcomes

Auditory Brainstem Response (ABR) to click

Time frame: Up to week 48

Achievement of a score ≥3 on the Early Speech Perception (ESP) test

Time frame: At week 104

Achievement of hearing sensitivity threshold of ≤45 dB assessed by average PTA

Time frame: Up to week 104

Achievement of hearing sensitivity threshold of ≤25 dB assessed by average PTA

Time frame: Up to week 104

Achievement of a score of 4 on the ESP test

Time frame: At week 104

Speech Awareness Threshold (SAT): achievement of a threshold of ≤70 dB

Time frame: Up to week 104

SAT: achievement of a threshold of ≤45 dB

Time frame: Up to week 104

SAT: achievement of threshold of ≤25 dB

Time frame: Up to week 104

Average PTA threshold in the subset of patients who achieved an average PTA threshold ≤70 dB

Time frame: Up to week 104

Average PTA threshold in the subset of patients who achieved an average PTA threshold >70 dB but ≤85 dB

Time frame: Up to week 48

Achievement of a hearing sensitivity threshold improvement of ≥10 dB from baseline

Time frame: Up to week 48

Time to an average PTA threshold ≤70 dB

Time frame: Up to week 104

Persistence of an average PTA threshold ≤70 dB

Time frame: Up to week 104

Incidence of patients who regress to >70 dB after having achieved average PTA threshold

Time frame: Up to week 104

Speech perception scores by age-appropriate tests

Time frame: Up to week 48

Severity in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)

Time frame: Up to week 48

Change in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)

Time frame: Up to week 48

Presence of auditory brainstem response (ABR) to click at ≤90 dB normalized Hearing Level (nHL)

Time frame: At week 104

Speech perception scores by age-appropriate tests (other than ESP)

Time frame: At week 104

Severity in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)

Time frame: At week 104

Change in speech perception ability assessed by Global Impression scales (clinician and parent/legal guardian)

Time frame: At week 104

Change from baseline on LittlEARS®

Time frame: At week 104

Change in scores on LittlEARS®

Time frame: At week 104

Change from baseline on Auditory Skills Checklist

Time frame: At week 104

Change in scores on Auditory Skills Checklist

Time frame: At week 104

Change from baseline on MacArthur-Bates Communicative Development Inventories (MB-CDI)-Words and Gestures

Time frame: At week 104

Change in scores on MB-CDI-Words and Gestures

Time frame: At week 104

Change from baseline on MB-CDI -Words and Sentences

Time frame: At week 104

Change in scores on MB-CDI -Words and Sentences

Time frame: At week 104

Change from baseline on MB-CDI-III Vocabulary and Grammar

Time frame: At week 104

Change in scores on MB-CDI-III Vocabulary and Grammar

Time frame: At week 104

Clinical assessments of speech production: articulation

Time frame: At week 104

Clinical assessments of speech production: speech intelligibility

Time frame: At week 104

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

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts