An Investigator Initiated Study for OTOV101N+OTOV101C Injection

NCT05901480 | Unknown

• 1 other identifier: OTOV101-IIT-101
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 23

Brief Summary

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).

Conditions

DFNB9

Outcome Measures

Primary Outcomes (13)

• Incidence and severity of adverse events (AEs)

  Incidence and severity of AEs are assessed by NCI-CTCAE 5.0.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Up to 12 months after unilateral cochlear injection

• Safety assessment by electrocardiogram

  Number and percentage of participants with abnormal ECG readings with clinical significance.

  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.

  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.

  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.

  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.

  Up to 12 months after unilateral cochlear injection

Secondary Outcomes (6)

• Efficacy assessment by Behavioral audiometry testing

  Up to 12 months after unilateral cochlear injection

• Efficacy assessment by ABR (Auditory Brainstem Response) testing

  Up to 12 months after unilateral cochlear injection

• Efficacy assessment by ASSR (Auditory Steady-state Response) testing

  Up to 12 months after unilateral cochlear injection

• Efficacy assessment by DPOAE (Distortion Product Otoacoustic Emission) testing

  Up to 12 months after unilateral cochlear injection

• Efficacy assessment by CM (Cochlear Microphonic) potential

  Up to 12 months after unilateral cochlear injection

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients with OTOF mutation-related deafness

Genetic: OTOV101N+OTOV101C Injections

Interventions

OTOV101N+OTOV101C Injections GENETIC

The gene therapy of OTOV101N+OTOV101C injection via intracochlear injection.

Treatment Arm

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 1 years old at the time of signing the informed consent form (ICF); both male and female are eligible.
• Diagnostic criteria for OTOF-related hearing loss are:
• The hearing test and auditory brainstem response (ABR) examination show the presence of hearing loss (based on the testing report conducted within one month prior to signing the informed consent form).
• Genetic testing confirms the presence of OTOF gene homozygous or compound heterozygous mutations.
• Hearing loss: severe (65 dB ≤ hearing threshold \< 80 dB) or profound (80 dB ≤ hearing threshold \< 95 dB) or total (hearing threshold ≥ 95 dB) hearing loss in both ears (If the testing result of ABR is "waveform is not obtained", the subjects with bilateral hearing threshold \<65 dB will be enrolled as determined by the investigator).
• Vital signs, physical examination, laboratory tests (including whole blood count, blood biochemistry, urinalysis, coagulation function, etc.), and 12-lead electrocardiogram are all normal, or any abnormalities judged by the investigator are clinically non-significant.
• The subjects and their guardians sign the informed consent form.

You may not qualify if:

• Subjects who have had a severe allergic reaction (NCICTCAE5.0 ≥ 3 Grade) to any drug or its components used in this study in the past;
• Subjects who have received any gene therapy in the past, or have high levels of neutralizing antibodies (\>1:128) in their blood;
• Subjects who have systemic diseases or are receiving related treatments that may affect hearing or surgical operations;
• Subjects who cannot tolerate anesthesia;
• Subjects with inner ear malformations;
• Subjects who have undergone bilateral cochlear implantation or have a history of major inner ear surgery (as determined by the investigator)(not include unilateral cochlear implantation);
• Subjects with other genetic mutations causing deafness that may affect the effectiveness of OTOF gene therapy;
• Subjects with Meniere's disease;
• Subjects who routinely use ototoxic drugs for other medical conditions;
• Subjects with congenital deafness caused by non-genetic factors related to birth;
• Subjects who are currently receiving or may receive immunosuppressive therapy other than this study;
• Subjects who are allergic or intolerant to glucocorticoid treatment;
• Subjects with a history of malignant tumors or meningitis;
• Subjects 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;
• Subjects 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;

Sponsors & Collaborators

• Otovia Therapeutics: lead

Study Sites (23)

Shandong Second Provincial General Hospital

Jinan, Shandong, 250023, China

RECRUITING

Beijing Tongren Hospital

Beijing, China

NOT YET RECRUITING

Beijing Union Hospital

Beijing, China

NOT YET RECRUITING

Chinese PLA Genreal Hospital

Beijing, China

NOT YET RECRUITING

The Third Bethune Hospital of Jilin University

Changchun, China

NOT YET RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, China

NOT YET RECRUITING

Sichuan Provincial People Hospital

Chengdu, China

NOT YET RECRUITING

Chongqing Municipal People Hospital

Chongqing, China

NOT YET RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, China

NOT YET RECRUITING

Guangdong Provincial People Hospital

Guangzhou, China

NOT YET RECRUITING

The First Affiliated Hospital of Harbin Medical University

Harbin, China

NOT YET RECRUITING

The First Affiliated Hospital of USTC

Hefei, China

NOT YET RECRUITING

The Second Affiliated Hospital of Anhui Medical University

Hefei, China

NOT YET RECRUITING

Yunnan Provincial First People Hospital

Kunming, China

NOT YET RECRUITING

Dongnan University Zhongda Hospital

Nanjing, China

NOT YET RECRUITING

Nanjing Drum Tower Hospital

Nanjing, China

RECRUITING

The Second Hospital of Ningbo

Ningbo, China

NOT YET RECRUITING

Shengjing Hospital Of China Medical University

Shenyang, China

NOT YET RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, China

NOT YET RECRUITING

Union Hospital of Tongji Medical College of Huazhong University of Science and Technology

Wuhan, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, China

NOT YET RECRUITING

Xijing Hospital

Xi'an, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

NOT YET RECRUITING

Related Publications (1)

• Qi J, Zhang L, Lu L, Tan F, Cheng C, Lu Y, Dong W, Zhou Y, Fu X, Jiang L, Tan C, Zhang S, Sun S, Song H, Duan M, Zha D, Sun Y, Gao X, Xu L, Zeng FG, Chai R. AAV gene therapy for autosomal recessive deafness 9: a single-arm trial. Nat Med. 2025 Sep;31(9):2917-2926. doi: 10.1038/s41591-025-03773-w. Epub 2025 Jul 2.

  PMID: 40603731 DERIVED

Study Officials

• Shanzhong Zhang, MD PhD

  Otovia Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Shanzhong Zhang, MD PhD

CONTACT

+86 18616595944; zhangshanzhong@fosunpharma.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: June 13, 2023
• Study Start: June 26, 2023
• Primary Completion: December 6, 2024
• Study Completion: February 18, 2025
• Last Updated: May 8, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (23)