Gene therapy for OTOF mutation-related deafness

An Investigator Initiated Study Evaluating the Safety, Tolerability, and Efficacy of OTOV101N+OTOV101C Injection in Treating Patients With OTOF Mutation-related Deafness

This study is testing a new gene therapy injection to see if it can help people with deafness caused by OTOF mutations regain their hearing.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 1 Year and up
• Sex: All
• Sponsor: Otovia Therapeutics (industry)
• Locations: 23 sites (Jinan, Shandong and 22 other locations)
• Trial ID: NCT05901480 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and efficacy of OTOV101N+OTOV101C injection in patients with OTOF mutation-related deafness. Participants will receive gene therapy via intracochlear injection and will be monitored for safety and efficacy at various time points throughout the study. The study involves a preparatory glucocorticoid treatment and hospitalization for observation post-injection. The goal is to assess the potential benefits of this gene therapy in restoring hearing.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 1 year and older with confirmed OTOF gene mutations and varying degrees of hearing loss.

Not a fit: Patients without OTOF mutations or those with hearing loss not meeting the specified criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve hearing in patients with OTOF mutation-related deafness.

How similar studies have performed: While gene therapy for hearing loss is a novel approach, similar studies have shown promise in other genetic conditions, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 1 years old at the time of signing the informed consent form (ICF); both male and female are eligible.
2. Diagnostic criteria for OTOF-related hearing loss are:

   1. 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).
   2. Genetic testing confirms the presence of OTOF gene homozygous or compound heterozygous mutations.
3. 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).
4. 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.
5. The subjects and their guardians sign the informed consent form.

Exclusion Criteria:

1. 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;
2. Subjects who have received any gene therapy in the past, or have high levels of neutralizing antibodies (\>1:128) in their blood;
3. Subjects who have systemic diseases or are receiving related treatments that may affect hearing or surgical operations;
4. Subjects who cannot tolerate anesthesia;
5. Subjects with inner ear malformations;
6. 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);
7. Subjects with other genetic mutations causing deafness that may affect the effectiveness of OTOF gene therapy;
8. Subjects with Meniere's disease;
9. Subjects who routinely use ototoxic drugs for other medical conditions;
10. Subjects with congenital deafness caused by non-genetic factors related to birth;
11. Subjects who are currently receiving or may receive immunosuppressive therapy other than this study;
12. Subjects who are allergic or intolerant to glucocorticoid treatment;
13. Subjects with a history of malignant tumors or meningitis;
14. 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;
15. 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;
16. Female subjects of childbearing age who have a positive blood pregnancy test result, or are currently pregnant or breastfeeding;
17. Subjects who 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. Subjects who are unwilling or unable to comply with this study protocol;
19. Subjects 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.

Where this trial is running

Jinan, Shandong and 22 other locations

• Shandong Second Provincial General Hospital — Jinan, Shandong, 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)

Study contacts

• Study coordinator: Shanzhong Zhang, MD PhD

Conditions: DFNB9