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Gene Therapy for Congenital Hearing Loss
(CHORD Trial)

Recruiting in Palo Alto (17 mi)

+21 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Cochlear implants, Malignancies, Meningitis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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)

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment DB-OTO for congenital hearing loss?

Research shows that gene therapy, like DB-OTO, has successfully restored hearing in animal models with genetic forms of deafness. For example, a study using a similar approach with dual AAV vectors restored hearing in mice with a specific type of genetic deafness, suggesting potential for human treatment.¹ ² ³ ⁴ ⁵

How is the treatment DB-OTO unique for congenital hearing loss?

DB-OTO is a novel gene therapy that uses a dual AAV (adeno-associated virus) approach to deliver the otoferlin gene, which is too large for a single AAV vector, directly into the cochlea. This method aims to restore hearing by addressing the genetic cause of deafness, unlike traditional treatments like cochlear implants that only bypass the damaged parts of the ear.¹ ² ³ ⁶ ⁷

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for children under 18 with profound sensorineural hearing loss due to OTOF gene mutations, who meet cochlear implant criteria and have not benefited from ear amplification. They must not have had previous gene therapy or cochlear implants in the affected ear(s), nor other untreatable hearing conditions.

Inclusion Criteria

My child's inner ear function is confirmed normal for DB-OTO treatment.

My child has severe hearing loss diagnosed by tests.

My child's ears can produce sounds in response to a test, and they are 24 months old or younger.

See 13 more

Exclusion Criteria

I have had meningitis before.

I have had cancer before or have it now.

My ear structure allows for the planned surgery based on my scans.

See 4 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive unilateral intracochlear dosing to evaluate safety and tolerability

4-6 weeks

Dose Expansion

Participants receive bilateral intracochlear dosing using the dose selected based on safety and efficacy data from the Dose Escalation phase

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

DB-OTO (Gene Therapy)

Trial OverviewDB-OTO, an AAV based gene therapy, is being tested on pediatric patients with biallelic OTOF mutations. The study has two parts: Part A tests increasing doses in patients, while Part B expands to more participants receiving the treatment bilaterally.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: DB-OTO - Dose ExpansionExperimental Treatment1 Intervention

Bilateral intracochlear dosing using the dose selected based on safety and efficacy data from the Dose Escalation phase (Part A).

Group II: DB-OTO - Dose EscalationExperimental Treatment1 Intervention

Unilateral intracochlear dosing

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:

The Nemours Foundation d/b/a Nemours Children's HealthOrlando, FL

UCLA Health- Department of MedicineLos Angeles, CA

The Nemours Foundation d/b/a Nemours Children's HealthJacksonville, FL

Children's Hospital Medical CenterCincinnati, OH

More Trial Locations

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Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Patients Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for sensorineural hearing loss.Chien, WW., Monzack, EL., McDougald, DS., et al.[2014]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model.Akil, O., Dyka, F., Calvet, C., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene transfer in inner ear cells: a challenging race.Sacheli, R., Delacroix, L., Vandenackerveken, P., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss.Bankoti, K., Generotti, C., Hwa, T., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetal gene therapy and pharmacotherapy to treat congenital hearing loss and vestibular dysfunction.Hastings, ML., Brigande, JV.[2021]

A novel gene therapy using a single overloaded adeno-associated virus (AAV) vector successfully delivered the full-length otoferlin gene to about 30% of inner hair cells in deaf otoferlin knock-out mice, showing promise for treating genetic hearing impairments.

This approach demonstrated partial restoration of hearing in the mice, suggesting that using a single AAV vector simplifies the gene transfer process compared to previous dual-AAV methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness.Rankovic, V., Vogl, C., Dörje, NM., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hearing of Otof-deficient mice restored by trans-splicing of N- and C-terminal otoferlin.Tang, H., Wang, H., Wang, S., et al.[2023]