A Clinical Trial of EHT102 Injection in Pediatric Patients With Biallelic hOTOF Mutations

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 study is a multicenter, single-arm, open-label Phase I/II clinical trial, which is designed to evaluate the safety, tolerability and efficacy of EHT102 injection in treating congenital hearing loss secondary to biallelic mutations of OTOF (DFNB9).Up to 30 pediatric participants (A maximum of 15 participants will be enrolled in each of the United States and China) will be enrolled and dosed with EHT102. The dose-escalation phase (Phase I) includes two predefined dose cohorts (3 participants per cohort), with sequential enrollment from low to high dose. During dose escalation, each participant will receive a unilateral EHT102 injection followed by safety observation.

Study Overview

• Status: Recruiting
• Conditions: Treatment of Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
• Intervention / Treatment: Drug: EHT102 Injection

Detailed Description

The low-dose and high-dose cohorts will be followed by a 28-day DLT observation period.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Minghui Huang, M.D; Phone Number: +86 18017315362; Email: minghui.huang@euhearing.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Eye & ENT Hospital of Fudan University
      • Contact: Yilai Shu, M.D. & Ph.D.; Phone Number: +86 021 64377134; Email: yilai_shu@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The low-dose cohort; Participants will receive a single unilateral or bilateral administration of EHT102 at the defined low dose level	Drug: EHT102 Injection; EHT102 injection is a dual-vector gene therapy product developed for the treatment of OTOF-related hearing loss.
Experimental: The high-dose cohort; Participants will receive a single unilateral or bilateral administration of EHT102 at the defined high dose level.	Drug: EHT102 Injection; EHT102 injection is a dual-vector gene therapy product developed for the treatment of OTOF-related hearing loss.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0	Safety will be evaluated by summarizing the number and percentage of participants experiencing treatment-related adverse events (TEAEs) and serious adverse events (SAEs). Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	Up to week 52
Proportion of Participants Achieving a Hearing Sensitivity Threshold of ≤70 dB by behavioral audiometry	This endpoint evaluates the efficacy of EHT102 injection by calculating the percentage of participants who achieve a hearing sensitivity threshold of ≤70 dB in the treated ear, as assessed by behavioral audiometry.	Up to week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Auditory Brainstem Response (ABR) Thresholds	The change from baseline in ABR thresholds will be assessed in the treated ear. ABR thresholds are measured in decibels (dB). The metric reported will be the change in the average threshold across frequencies (0.5, 1, 2, and 4 kHz) from baseline to each post-treatment time point.	Week 4, Week 13, Week 26, and Week 52
Change from baseline in auditory steady state response (ASSR) thresholds	This endpoint assesses the change from baseline in Auditory Steady-State Response (ASSR) thresholds in the treated ear. The metric reported will be the mean change in threshold (in dB) across available frequencies from baseline to each post-treatment time point.	Week 4, 13, 26, and 52
Proportion of Participants of a hearing sensitivity threshold of ≤70 dB assessed by behavioral audiometry	This endpoint evaluates the efficacy of EHT102 injection at additional timepoints by calculating the percentage of participants who achieve a hearing sensitivity threshold of ≤70 dB in the treated ear, as assessed by behavioral audiometry.	Week 4, 13 and 52
Proportion of Participants of a hearing sensitivity threshold of ≤45 dB assessed by behavioral audiometry at Week 26 post injection	This endpoint evaluates a higher efficacy threshold by calculating the percentage of participants who achieve a hearing sensitivity threshold of ≤45 dB in the treated ear at Week 26, as assessed by behavioral audiometry	Week 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-determined drug/procedure related AEs and SAEs occurring during Years 1-5 post injection	Long-term safety will be assessed by monitoring the incidence of adverse events (AEs) and serious adverse events (SAEs) that are determined by the investigator to be related to the study drug and/or the surgical procedure during the long-term follow-up period.	Years 1 through 5

Collaborators and Investigators

• Sponsor: Shanghai Euhearing Therapeutics Co., Ltd
• Investigators: Principal Investigator: Yilai Shu, M.D. & Ph.D., Eye & ENT Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2033

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: OTOF
• Other Study ID Numbers: EHT102USCL01; EHT102CNCL02 (Registry Identifier: China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. The data generated in this Phase I/II study are proprietary. Aggregate safety and efficacy data will be reported in clinical study reports and potential publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No