a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)

Early Phase 1

Withdrawn

• Conditions: Congenital Hearing Loss
• Interventions: Genetic: HG205

• Registration Number: NCT06025032
• Lead Sponsor: HuidaGene Therapeutics Co., Ltd.

Brief Summary

The purpose of the study is to determine whether HG205 as CRISPR/Cas13 RNA base-editing therapy is safe and effective for the treatment of hearing loss caused by p.Q829X mutation in OTOF gene.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-30
• Study First Submitted: 2023-08-21
• Study First Submitted QC: 2023-08-29
• Study First Posted: 2023-09-06
• Status Verified: 2025-03
• Primary Completion: 2025-04-08
• Study Completion: 2025-04-08
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Male or females between 1 and 16 years of age at the time the subject/parent/legal guardian signs the informed consent form.
• Willing to adhere to the protocol as evidenced by written informed consent or parental permission and subject assent.
• Molecular diagnosis of biallelic mutations in the OTOF gene with at least one mutation being p.Q829X through collected blood samples at screening;
• Based on auditory brainstem response (ABR), clinically diagnosed sensorineural hearing loss (SNHL) with the following hearing thresholds: severe (65 dB ≤ hearing threshold < 80 dB) or profound (80 dB ≤ hearing threshold < 95 dB) or complete (hearing threshold ≥ 95 dB) hearing loss in both ears.
• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

Exclusion Criteria

• Pre-existing other hearing-loss conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or complications of surgery.
• Presence of cochlear implants in the study ear.
• Complicating systemic diseases or clinically significant abnormal baseline laboratory values.
• Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter hearing function.
• Prior participation in clinical study with an investigational drug within the past six months.
• Prior gene therapy treatments.
• Any condition which leads the investigator to believe that the participant cannot comply with the protocol requirements or that may place the participant at an unacceptable risk for participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HG205	HG205	Method of Administration: Once Unilateral intracochlear injection/subject; The duration of the study for each subject includes a screening period, enrollment visit, treatment visit, a 26-week follow-up period, and a 5-year long-term safety follow-up after the injection

Primary Outcome Measures

Name	Time	Method
Incidence of otological and systemic adverse events	26 weeks	Number of AE(Adverse events),SAE(Serious Adverse Events),DLT(Dose Limiting Toxicities)

Secondary Outcome Measures

Name	Time	Method
Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])	26 weeks	ABR intensity threshold (decibels normal hearing level \[dB nHL\]) measurement
Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry	26 weeks	Behavioral audiometry and pure-tone audiometry measurement

Trial Locations

Locations (2)

Eye & ENT Hospital of Fudan University; 🇨🇳 Shanghai, China

Eye & ENT Hospital of Fudan University; 🇨🇳 Shanghai, China