Hereditary deafness caused by GJB2 gene mutation
Conditions
Interventions
Low dose group:Administration was performed via round window injection of a low dose of EHT201, an AAV-based gene therapy carrying the coding sequence for the normal human GJB2 gene
Medium dose group:Administration was performed via round window injection of a medium dose of EHT201, an AAV-based gene therapy carrying the coding sequence for the normal human GJB2 gene
High dose group:Administration was performed via round window injection of a high dose of EHT201, an AAV-based gene therapy carrying the coding sequence for the normal human GJB2 gene
Sponsors
Eye & ENT Hospital of Fudan University
Eligibility
Sex/Gender
All
Age
0.5 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.The subject and/or their legal guardian must provide informed consent prior to participation, voluntarily sign the written informed consent form, and be willing to comply with all scheduled follow-up visits; 2. Ability to communicate effectively with the investigator with the assistance of a guardian and adhere to study requirements. For young children without mature language skills, ability to cooperate with the assistance of a guardian and comply with the investigator's requirements; 3.The subject and/or guardian have a correct understanding of the trial and possess appropriate expectations regarding potential benefits; 4. Age >= 6 months, any gender; 5. Documented genetic diagnosis of hearing loss due to GJB2 mutations: homozygous or compound heterozygous mutations; 6. Audiological criteria: severe or profound hearing loss (>=65 dB); 7. Meet otologic surgical requirements: Exclusion of conditions incompatible with the procedure (e.g., severe middle-inner ear malformations, cochlear nerve dysplasia) via CT and/or MRI scan within 3 months of screening; confirmation of surgical eligibility.
Exclusion criteria
Exclusion criteria: 1. Genetic diagnosis does not indicate GJB2 mutations; 2. Other types of hearing loss unsuitable for the specified otologic surgery, such as severe middle-inner ear malformations or cochlear nerveabnormalities identified on CT/MRI within 3 months; 3. Pre-existing otologic conditions that would impede the planned surgery or interfere with endpoint interpretation (e.g., acute/chronic otitis media, Ménière's disease, acoustic neuroma, unresolved sudden sensorineural hearing loss); 4. History of drug abuse; treatment with any known ototoxic medications within 6 months (e.g., aminoglycosides, cisplatin, loop diuretics); or receipt of antiviral/immunotherapy within 3 months; 5.Severely immunocompromised individuals, history of significant immunodeficiency (including HIV positivity, other acquired/congenital immunodeficiency diseases), or history of organ transplantation; 6. Severe systemic diseases or acute conditions (e.g., tuberculosis, active hepatitis B/C, active herpes zoster infection, pancreatitis, renal insufficiency, gastrointestinal ulcer); 7. Contraindications to surgery or anesthesia, as determined by the surgeon, anesthesiologist, or designee, including but not limited to cardiovascular or cerebrovascular events within the previous 6 months (e.g., myocardial infarction, heart failure, angina, cerebrovascular accident, or transient ischemic attack), any other cardiac condition judged by the investigator to render the subject unsuitable for participation in this trial, or hypersensitivity/allergy to any planned medication; 8. Presence of implants in the operative ear at screening (e.g., cochlear implant); 9. Coexisting other severe congenital disorders; 10. History of significant neurological or psychiatric disorders (e.g., epilepsy, dementia) not adequately controlled; 11. Any other condition deemed by the investigator to make the subject unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs);Incidence and severity of Serious Adverse Events (SAEs) or Adverse Events (AEs);Vital signs assessment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Behavioral Audiometry;Auditory Brainstem Response (ABR);Auditory Steady-State Response (ASSR);Distortion Product Otoacoustic Emissions (DPOAE);Speech Recognition;Laboratory examination: blood biochemistry, coagulation function, routine blood/urine tests, anti AAV neutralizing antibody, ELISpot, blood qPCR test for AAV shedding;Specialist physical examination: external ear and ear canal, tympanic membrane, tympanic cavity, mastoid process;Assessment of vestibular function;Imaging examination; | — |
Countries
China
Contacts
Public ContactYilai Shu
Eye & ENT Hospital of Fudan University
Outcome results
None listed