EHT102 injections for children with OTOF-related congenital deafness

A Phase Ⅰ/Ⅱ, Multicenter, Single-arm, Open-label Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of EHT102 Injection in Pediatric Patients With Biallelic hOTOF Mutations

This trial will try a single unilateral EHT102 injection in children aged 1–17 who have congenital deafness from two OTOF gene mutations to see if it is safe and helps hearing.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 1 Year to 17 Years
• Sex: All
• Sponsor: Shanghai Euhearing Therapeutics Co., Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07288580 on ClinicalTrials.gov

What this trial studies

This multicenter, single-arm, open-label Phase I/II trial will test EHT102 delivered as a unilateral inner-ear injection in pediatric patients with DFNB9 due to biallelic OTOF mutations. Up to 30 children aged 1–17 will be enrolled, with a maximum of 15 participants planned in each of the United States and China and sequential dosing from low to high. Phase I includes two predefined dose cohorts (three participants per cohort) with a 28-day dose-limiting toxicity (DLT) observation period after dosing. Participants will undergo close safety monitoring and audiologic assessments to detect tolerability signals and any changes in hearing over follow-up.

Who should consider this trial

Good fit: Children aged 1–17 with confirmed biallelic OTOF (DFNB9) mutations and severe-to-profound hearing loss (≥65 dB) whose guardians can provide informed consent and commit to follow-up are ideal candidates.

Not a fit: Patients who do not have biallelic OTOF mutations, have milder hearing loss, have other non-OTOF causes of deafness (for example cochlear nerve deficiency), or cannot attend the participating centers are unlikely to benefit.

Why it matters

Potential benefit: If successful, EHT102 could restore or improve natural hearing in children with OTOF-related congenital deafness, potentially reducing reliance on cochlear implants or other assistive devices.

How similar studies have performed: Preclinical work and early gene-therapy research targeting OTOF have shown promising results in animal models, but human clinical evidence is still limited and the approach remains largely experimental.

Eligibility criteria

Key Inclusion Criteria:

1. Prior to study participation, participants and/or their legal guardians must provide informed consent for this trial, voluntarily sign the written informed consent form (ICF), and commit to completing all protocol-specified follow-up visits;
2. Participants must be able to communicate effectively with investigators and comply with study requirements, with guardian assistance if needed. For young children without developed language skills, guardians must ensure cooperation with investigator instructions;
3. Participants and/or their legal guardians must demonstrate adequate comprehension of the trial's nature and maintain realistic expectations regarding potential benefits.
4. Pediatric patients (male or female) aged ≥ 1 and ≤ 17 years at the time of inclusion ;
5. Genetic testing report indicates DFNB9 congenital deafness with Biallelic mutations in the Otoferlin gene;
6. Severe or profound hearing loss (≥65 dB) assessed by ABR, with the sentinel participant having an ABR \>90 dB;
7. Meet eligibility criteria for otologic surgery: Absence of middle/inner ear malformations, cochleovestibular nerve abnormalities, or active otologic inflammation as confirmed by computed tomography (CT) and/or magnetic resonance imaging (MRI) within 3 months or during screening period, with surgical suitability determined by the investigator;
8. DPOAE testing shows present response.

Exclusion Criteria:

1. Have other types of hearing loss ineligible for otologic surgery, including but not limited to:

   Middle/inner ear malformations or developmental abnormalities identified by CT/MRI within 3 months; Hearing loss caused by cochleovestibular nerve abnormalities; Conductive hearing loss ; Mixed hearing loss; Syndromic deafness with malformations.
2. Have pre-existing otologic conditions deemed by the investigator to potentially compromise the planned surgery or interfere with study endpoint evaluation, including but not limited to:

   Acute/chronic otitis media;; Ménière's disease; Acoustic neuroma; Unresolved sudden sensorineural hearing loss.
3. Have a history of drug abuse.
4. Have a history of receiving any known ototoxic medications (e.g., aminoglycosides, cisplatin, loop diuretics) within the past 6 months.
5. Antiviral/immunotherapy within 3 months prior to screening.
6. Administration of any live-attenuated vaccines within 30 days prior to screening.
7. Have immunocompromised status or immunodeficiency disorders, including but not limited to:

   Positive HIV antibody (HIV Ab) test; Congenital or acquired immunodeficiency (investigator-determined contraindication to immunosuppressants) ; History of organ transplantation.
8. Have severe systemic diseases or acute conditions, including but not limited to:

   Active tuberculosis; Active herpes zoster infection; Pancreatitis; Renal insufficiency; Gastrointestinal ulcers.
9. Have contraindications to surgery or anesthesia as determined by the surgeon, anesthesiologist, or designated personnel, including but not limited to:

   History of cardiovascular or cerebrovascular events within the past 6 months (e.g., myocardial infarction, heart failure, angina, stroke, or transient ischemic attack) Any other cardiac conditions deemed unsuitable for study participation by the investigator; Known hypersensitivity to the investigational drug.
10. Have participated in gene therapy trials within 6 months prior to screening, plan to participate in other interventional clinical trials within one year post-treatment, or have received investigational drugs within 5 half-lives of the last dose from previous trials.
11. Have implantable devices (e.g., cochlear implants) in the target ear at screening.
12. Have other severe congenital disorders.
13. Have a history of neurological/psychiatric disorders (e.g., epilepsy, dementia).
14. Have chronic anticoagulant therapy that cannot be temporarily discontinued.
15. Have a history of radiotherapy/chemotherapy deemed by investigators to potentially affect trial outcomes.
16. Have tested positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis C virus (HCV) antibody with HCV RNA positive, or positive for human immunodeficiency virus (HIV) antibody, or have active syphilis (TPPA positive and RPR positive).
17. Females of childbearing potential with positive pregnancy tests prior to dosing; Females of childbearing potential and non-sterilized males with fertile partners unwilling/unable to use effective contraception from ICF signing until ≥24 months post-dosing.
18. Any other condition that, at the discretion of the investigator, renders the participant unsuitable for enrollment.

Where this trial is running

Shanghai, Shanghai Municipality

• Eye & ENT Hospital of Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yilai Shu, M.D. & Ph.D. — Eye & ENT Hospital of Fudan University
• Study coordinator: Minghui Huang, M.D

Conditions Treatment of Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene; OTOF