The safety, tolerability, and preliminary efficacy of RRG-003 AAV in the treatment of DFNB9 congenital deafness

Phase 1

Recruiting

• Conditions: Congenital deafness

• Registration Number: ChiCTR2200063181
• Lead Sponsor: Eye & ENT Hospital of Fudan University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Patients and their guardians must voluntarily sign the informed consent prior to the trial, and are willing to be followed up at the time points specified in the trial;<br>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;<br>3. The subject's guardian has a proper understanding of the trial and an appropriate expectation of benefit;<br>4. Age >=6 months, without gender limitation;<br>5. According to the genitic test report, patients have either homozygous or compound heterozygous mutations in OTOF and were diagnosed with DFNB9 congenital deafness;<br>6. Audiology inclusion criteria: severe to complete deafness (>=65 dB);<br>7. To meet surgical qualification, middle - inner ear malformations, vestibulo-cochlear nerve abnormalities, ear inflammation, etc., should be excluded by CT scan and/or MRI scan within 3 months or at screening.<br>

Exclusion Criteria

1. Genetic diagnosis did not indicate OTOF mutations or simultaneous deafness caused by other gene mutations;<br>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 middle inner ear dysplasia or malformations, vestibular cochlear nerve abnormalities caused deafness, conductive deafness, mixed deafness, and malformation syndrome;<br>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;<br>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, or have been vaccinated within 1 month;<br>5. Individuals with low immunity and a history of immune deficiency, including HIV testing positive, other acquired or congenital immune deficiency diseases, or a history of organ transplantation;<br>6. Patients 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;<br>7. Patients 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;<br>8. Currently participating in or preparing to participate in any intervention clinical trials involving drugs or devices within 1 year of administration, or participating in other clinical trials within 5 half-lives after the last administration;<br>9. During screening, implants (such as cochlear implants) are present in the ear (on the same side of the intended surgery);<br>10. Neutralizing antibody titer for AAV1>1:2000;<br>11. Accompanied by other serious congenital diseases;<br>12. Has a clear history of neurological or mental disorders, including epilepsy or dementia;<br>13. Patients who need to take anticoagulants for a long time but cannot pause in the short term;<br>14. History of radiation and chemotherapy;<br>15. The researchers identify that the subjects are not suitable in this clinical study for any other situations.

Study & Design

• Study Type: Interventional study
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity within 6 weeks;

Secondary Outcome Measures

Name	Time	Method
Laboratory examination: blood biochemistry, coagulation function, hematuria routine, anti AAV neutralizing antibody, ELISpot, blood qPCR test for AAV shedding;Pure tone audiometry, PTA;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;