An interventional study of OTOV101N+OTOV101C Injections in DFNB9, sponsored by Otovia Therapeutics. Recruiting at 23 sites in China. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2024-05-08.
Sponsored by Otovia Therapeutics · Not applicable, Interventional, and Treatment
This study is an investigator initiated study to evaluate the safety, tolerability, and efficacy of OTOV101N+OTOV101C injection in treating patients with OTOF mutation-related deafness. The enrolled subjects who meet the inclusion and exclusion criteria will receive the gene therapy of OTOV101N+OTOV101C injection via intracochlear injection. All participants will return to the hospital for safety and efficacy evaluations at predetermined time points defined by protocol during the study (Week 1 ± 1 Day, Week 2 ± 3 Days, Week 3 ± 3 Days, Month 1 ± 3 Days, Month 2 ± 3 Days, Month 4 ± 6 Days, Month 6 ± 6 Days, Month 9 ± 6 Days, Month 12 ± 6 Days/EOS (end of study)/unscheduled visit).
This study is an investigator initiated study to evaluate the safety, tolerability, and efficacy of OTOV101N+OTOV101C injection in treating patients with OTOF mutation-related deafness.
Subjects who are successfully enrolled will visit the hospital on Day -3 to initiate the glucocorticoid treatment, then be hospitalized on Day -3\~-1 to prepare for inner ear gene therapy. On the day of surgery (Day 0), subjects will undergo intracochlear injection of gene therapy products after skin preparation and disinfection of the surgical area and general anesthesia. The round window will be exposed through the tympanic membrane route. Each subject will receive adeno-associated virus (AAV) injection at a dose of 15\~30μL of each AAV, mixed at 1: 1 ratio with total volume of 30\~60 μL/ear. For subjects without any cochlear implantation, bilateral or unilateral intracochlear injection could be conducted as decided by investigators. For intracochlear injection, the investigators will decide if the second intracochlear injection should be conducted based on dose of the first injection by considering anatomical structure of artificial cochlea and drug loss. The timing of the second injection will be decided by recovery status of the first injection. Subjects will be in hospital for 3 days for observation after receiving the intracochlear injection or follow the routine hospitalization timing of diagnosis/treatment of site, then be discharged after recovery from the surgical operation and receive 1 year follow-up visits.
All subjects will return to the hospital (except in case of non-resistance) for safety and efficacy assessments during the study at the established time points in the protocol (Week 1 ± 1 Day, Week 2 ± 3 Days, Week 3 ± 3 Days, Month 1 ± 3 Days, Month 2 ± 3 Days, Month 4 ± 6 Days, Month 6 ±6 Days, Month 9 ± 6 Days, Month 12 ± 6 Days/EOS (end of study)/Unscheduled) unless encountering force majeure.
This is the only study on the registry with Otovia Therapeutics as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Diagnostic criteria for OTOF-related hearing loss are:
Exclusion Criteria:
Patients with OTOF mutation-related deafness
Genetic: OTOV101N+OTOV101C Injections
The gene therapy of OTOV101N+OTOV101C injection via intracochlear injection.
Incidence and severity of adverse events (AEs)
Incidence and severity of AEs are assessed by NCI-CTCAE 5.0.
Time frame: Up to 12 months after unilateral cochlear injection
Drug-relatedness of adverse events (AEs)
Drug-relatedness of AEs include definitely relevant, probably relevant, possible relevant, possible irrelevant, and definitely irrelevant.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by physical examination
Number and percentage of participants with abnormal physical examination findings with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by whole blood count
Number and percentage of participants with abnormal laboratory test results (whole blood count) with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by urinalysis
Number and percentage of participants with abnormal laboratory test results (urinalysis) with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by blood biochemistry testing
Number and percentage of participants with abnormal laboratory test results (blood biochemistry testing) with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by coagulation function testing
Number and percentage of participants with abnormal laboratory test results (coagulation function) with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by vital signs
Number and percentage of participants with abnormal vital signs with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by electrocardiogram
Number and percentage of participants with abnormal ECG readings with clinical significance.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by cranial MRI (Magnetic Resonance Imaging)
Changes in cranial MRI relative to baseline, to observe possible signs of infection after gene therapy on inner ear. The MRI conduction is decided by investigator.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by neutralizing antibodies in peripheral blood
Changes in neutralizing antibodies relative to baseline in peripheral blood collections. Concentrations of neutralizing antibodies are analyzed by cell-mediated assay in vitro.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by Adeno-Associated Virus (AAV) in peripheral blood
Changes in AAV signals relative to baseline in peripheral blood collections. AAV signals are analyzed by real-time PCR assay in vitro.
Time frame: Up to 12 months after unilateral cochlear injection
Safety assessment by CT (Computed Tomography)
Changes in cranial CT relative to baseline, to observe possible signs of infection after gene therapy on inner ear. The CT conduction is decided by investigator.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by Behavioral audiometry testing
Changes in hearing assessment by behavioral audiometry relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. Behavioral audiometry assessments are to measure the hearing threshold at different frequencies (pitches) after treatment compared to its baseline values.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by ABR (Auditory Brainstem Response) testing
Changes in hearing assessment by ABR relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. ABR assessments are to measure the electrical response evoked by acoustic stimuli as sound signal is processed along the auditory pathway. Mean ABR air and bone conduction threshold are assessed.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by ASSR (Auditory Steady-state Response) testing
Changes in hearing assessment by ASSR relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. ASSR assessments are to measure the Steady-State electroencephalic response evoked by acoustic stimuli as sound signal is processed along the auditory pathway. Mean ASSR air and bone conduction threshold are assessed.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by DPOAE (Distortion Product Otoacoustic Emission) testing
Changes in hearing assessment by DPOAE relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. DPOAE is defined as sound generated within the cochlear by stimulating the ear with two simultaneous tones of different frequency. DPOAEs serve as an objective measure of hearing sensitivity. Tones will be played from low to high frequencies at soft to moderate levels to assess responses at different regions of the inner ear. DP levels will be recorded for each frequency and ear. Higher DP levels indicate more sensitive hearing. Change from baseline values will be calculated as the reported DP level value minus the baseline value. A negative change from baseline indicates less sensitive hearing.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by CM (Cochlear Microphonic) potential
Changes in hearing assessment of CM potentials relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. CM potentials are measured by Cochlear Response Telemetry System.
Time frame: Up to 12 months after unilateral cochlear injection
Efficacy assessment by tympanometry
Changes in hearing assessment of tympanometry relative to baseline, to observe the improvement of hearing functions after gene therapy on inner ear. Tympanometry are used to assess the mobility of the eardrum. Compliance, middle ear pressure and ear canal volume will be recorded and checked to measure function of middle ear and eustachian tube.
Time frame: Up to 12 months after unilateral cochlear injection
Plan to share: No
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.