A Study of EH002 Gene Therapy for Otoferlin Gene Mutation-mediated Hearing Loss

Inclusion Criteria:

1. The participant and/or their legal guardian must provide informed consent before thestudy, voluntarily sign the written informed consent form, and be willing to attendfollow-up visits as scheduled by the study.

2. The participant must communicate effectively with the investigator and comply withthe investigator's requirements, with the assistance of a legal guardian ifnecessary. Young children without mature language skills must be able to cooperateand comply with the investigator's requirements with the help of a legal guardian.

3. The participant and/or legal guardian must understand the study correctly and haveappropriate expectations regarding the potential benefits.

4. The participant must be at least 6 months old, with no restrictions on gender.

5. The participant must be diagnosed with DFNB9 congenital deafness, confirmed bygenetic testing showing homozygous or compound heterozygous mutations in the OTOFgene.

6. Audiological inclusion criteria: Severe or profound hearing loss (≥65 dB).

7. The participant must meet the surgical requirements, including the absence ofmiddle- or inner-ear malformations, vestibulocochlear nerve developmentalabnormalities, and ear inflammation, as confirmed by CT or MRI scans within 3 monthsor at the time of screening. Additionally, the participant must be deemed eligiblefor surgery.

Exclusion Criteria:

1. The genetic diagnosis does not indicate an OTOF mutation.

2. Other types of deafness that are unsuitable for otological surgery, such as middle-or inner-ear developmental abnormalities or malformations, vestibulocochlear nerveabnormalities, conductive hearing loss, mixed hearing loss, or malformationsyndromes, as detected by CT or MRI scans within 3 months.

3. Pre-existing otological conditions that would interfere with the planned surgery orthe interpretation of study endpoints, such as acute or chronic otitis media,Meniere's disease, acoustic neuroma, or unrecovered sudden sensorineural hearingloss.

4. A history of substance abuse, or treatment with any known ototoxic drugs (e.g.,aminoglycosides, cisplatin, loop diuretics) within the last 6 months, or antiviralmedications or immunotherapy within the last 3 months, or vaccination within thelast month.

5. Individuals with compromised immunity or a history of immunodeficiency, includingHIV-positive status, other acquired or congenital immunodeficiency disorders, or ahistory of organ transplantation.

6. Patients with severe systemic diseases or severe acute illnesses, such astuberculosis, active hepatitis B or C infection, active herpes zoster infection,pancreatitis, renal insufficiency, or gastrointestinal ulcers.

7. Patients with surgical or anesthetic contraindications as determined by the surgeon,anesthesiologist, or designated personnel. This includes those who have had acardiovascular or cerebrovascular event within the last 6 months, such as myocardialinfarction, heart failure, angina, stroke, transient ischemic attack, or any othercardiac condition deemed unsuitable by the investigator or an allergy to any plannedmedications.

8. Currently participating in or planning to participate in any interventional clinicaltrial involving drugs or devices within the next year or having received the lastdose of another clinical trial within 5 half-lives.

9. Presence of an implant in the ear (on the side intended for surgery) at the time ofscreening, such as a cochlear implant.

10. Neutralizing antibody titer against AAV1 >1:2000.

11. Presence of other severe congenital disorders.

12. A history of definite neurological or psychiatric disorders, including epilepsy ordementia.

13. Patients requiring long-term anticoagulant therapy that cannot be temporarilydiscontinued.

14. A history of chemotherapy or radiation therapy.

15. Any other condition that, in the opinion of the investigator, makes the participantunsuitable for this clinical study.