Pediatric and adult patients with severe or extremely severe hearing loss due to OTOF deficiency.
Conditions
Interventions
Low dose group:Administration of low dose AAV
High dose group:Administration of high dose AAV
Sponsors
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
1 Years to 28 Years
Inclusion criteria
Inclusion criteria: 1. Age >=12 months when signs the ICF, without gender limitation; 2. According to the genetic test report (test reports within 6 months prior to signing the ICF are acceptable), patients have either homozygous or compound heterozygous mutations in OTOF gene; 3. Patients must have severe or extremely severe hearing loss (Click ABR=80dBnHL); 4. Vital signs, physical examination, laboratory tests (including routine blood test, blood biochemistry, urinalysis, coagulation function, etc.), and 12-lead electrocardiogram are all normal, or any abnormalities judged by the investigator are clinically non-significant. 5. Patients and/or their guardians must voluntarily sign the informed consent prior to the trial.
Exclusion criteria
Exclusion criteria: 1. Genetic diagnosis shows gene deficiency other than OTOF that may cause the deafness symptom, which may affect the evaluation of effectiveness of the study drug. 2. Had a severe allergic reaction to any drug or its components used in this study in the past; 3. Have received any gene therapy and/or oligonucleotide drug therapy in the past; 4. Have high levels of AAV2 neutralizing antibodies (>1:2000) in the blood; 5. Have systemic diseases or are receiving related treatments that may affect hearing or surgical operations; 6. Patients who cannot tolerate anesthesia; 7. Have undergone bilateral cochlear implantation or have a history of major inner ear surgery (as determined by the investigator); 8. Other types of deafness that are not suitable for otological surgery, such as: the CT/MRI scan found that there were middle inner ear dysplasia or malformations, vestibular cochlear nerve abnormalities caused deafness, conductive deafness, mixed deafness, and malformation syndrome; 9. 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; 10. 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, or have been vaccinated within 1 month; 11. Patients who are currently receiving or may receive immunosuppressive therapy other than this study; 12. Patients who are allergic or intolerant to glucocorticoid treatment; 13. Have a history of malignant tumors or meningitis; 14. Patients with a persistent or active infection, positive for hepatitis B surface antigen (HBsAg) with peripheral blood HBV DNA titers higher than the detection limit, positive for hepatitis C virus (HCV) antibodies with peripheral blood HCV RNA titers higher than the detection limit, positive for human immunodeficiency virus (HIV) antibodies, or with other immune deficiency diseases, or positive for syphilis; 15. Patients of childbearing potential who refuse to take effective contraceptive measures (hormonal or barrier methods or abstinence) from the time of signing the informed consent form until 12 months after receiving AAV injection; 16. Female patients of childbearing age who have a positive blood pregnancy test result, or are currently pregnant or breastfeeding; 17. Have participated in any other clinical trial and have received treatment or medication within 4 weeks prior to the first administration (excluding non-interventional studies); 18. Patients who are unwilling or unable to comply with this study protocol; 19. Patients whom the investigator believes are unable to participate in this study due to any medical condition or who are unable to complete the follow-up study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation indicators: physical examination, vital signs, electrocardiogram, routine blood test, blood biochemistry, urinalysis, coagulation function, test of blood AAV neutralizing antibody level, test of blood AAV genome level, adverse events, serious adverse events, dose-limiting toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Behavioral audiometry;Auditory brainstem response;Pure-tone audiometry;Tympanogram;Distortion product otoacoustic emission (DPOAE);Cochlear microphonic;Auditory steady-state evoked responses;Sound source localization;Electroencephalogram;Speech recognition;Assessment of vestibular function;Functional imaging with near-infrared light;Growth and development and cognitive assessment;Electrocochleogram;Functional MRI;Magnetoencephalography;MRI of ear, vestibular, and brain;Middle-inner ear CT; | — |
Countries
China
Contacts
Public ContactHao Wu
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed