Congenital deafness
Conditions
Interventions
30 µl dose group:AAV-mediated gene therapy carrying normal OTOF gene via round window injection
50 µl dose group :AAV-mediated gene therapy carrying normal OTOF gene via round window injection
70 µl dose group:AAV-mediated gene therapy carrying normal OTOF gene via round window injection
140 µl dose group:AAV-mediated gene therapy carrying normal OTOF gene via round window injection
210 µl dose group:AAV-mediated gene therapy carrying normal OTOF gene via round window injection
Sponsors
Eye & ENT Hospital of Fudan University
Eligibility
Sex/Gender
All
Age
0.5 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Participants and/or their legal guardians must be fully informed about the study, voluntarily sign the informed consent form prior to the trial, and be willing to follow up at the time points specified in the trial; 2. Be able to communicate well with the researcher with the help of the guardian and comply with the requirements of the researcher. For children without mature language ability, they can cooperate and comply with the requirements of the researcher with the help of the guardian; 3. The subject's guardian has a proper understanding of the trial and an appropriate expectation of benefit; 4. Age >=6 months, without gender limitation; 5. According to the genitic test report, participants have either homozygous or compound heterozygous mutations in OTOF and were diagnosed with DFNB9 congenital deafness; 6. Audiology inclusion criteria: severe to complete deafness (>=65 dB); 7. To meet surgical qualification, severe middle - inner ear malformations, cochlear nerve abnormalities, etc., should be excluded by CT scan and/or MRI scan within 3 months or at screening.
Exclusion criteria
Exclusion criteria: 1. Genetic diagnosis did not indicate OTOF mutations; 2. Other types of deafness that are not suitable for otological surgery, such as: the CT/MRI scan within three months found that there were severe middle inner ear dysplasia or malformations, cochlear nerve abnormalities caused deafness,etc.; 3. Preexisting ear diseases may hinder the planned surgery or interfere with the interpretation of research endpoints, such as acute chronic otitis media, Meniere's disease, acoustic neuroma, sudden deafness, and unrecovered hearing; 4. Have a history of drug abuse, or have received any known ototoxicity drug treatment (such as aminoglycosides, cisplatin, loop diuretics, etc.) within 6 months, or have received antiviral and immunotherapy within 3 months; 5. Individuals with severe low immunity and a history of severe immune deficiency, including HIV testing positive, other acquired or congenital immune deficiency diseases, or a history of organ transplantation; 6. Participants with severe systemic diseases or severe acute phase diseases, such as pulmonary tuberculosis, active hepatitis B or C infection, active herpes zoster infection, pancreatitis, renal insufficiency, or gastrointestinal ulcers; 7. Participants with contraindications to surgery or anesthesia identified by surgeons, anesthesiologists, or designated personnel. If a cardiovascular or cerebrovascular accident occurs within the past 6 months, including myocardial infarction, heart failure, angina pectoris, cerebrovascular accident or transient ischemic attack, and any other heart disease judged by the researcher to be unsuitable for participation in this trial; or if they are allergic to the planned medication; 8. During screening, implants (such as cochlear implants) are present in the ear (on the same side of the intended surgery); 9. Accompanied by other serious congenital diseases; 10. Has a clear history of neurological or mental disorders, including epilepsy or dementia, whose condition is not currently adequately controlled; 11. The researchers identify that the subjects are not suitable in this clinical study for any other situations. Note Regarding Exceptions: Participants meeting certain exclusion criteria may still be considered for enrollment if a thorough evaluation confirms surgical tolerance with acceptable risk, and after full communication of potential risks and benefits with the participant and/or their legal guardian.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity within 6 weeks;Vital signs assessment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Laboratory examination: blood biochemistry, coagulation function, hematuria routine, anti AAV neutralizing antibody, ELISpot, blood qPCR test for AAV shedding;Behavioral Audiometry;Auditory brainstem evoked response, ABR;Auditory steady-state evoked responses, ASSR;Distortion Product Otoacoustic Emission, DPOAE;Speech recognition;Specialist physical examination: external ear and ear canal, tympanic membrane, tympanic cavity, mastoid process;Assessment of vestibular function;Adverse events;CT/MR Image; | — |
Countries
China
Contacts
Public ContactYilai Shu, Huawei Li
Affiliated Eye and ENT Hospital of Fudan University
Outcome results
None listed