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

NCT06025032 | Withdrawn Early Phase 1

• 1 other identifier: HG20501
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Hearing Loss

Keywords

Congenital hearing loss; OTOF; Q829X; HG205; CRISPR

Outcome Measures

Primary Outcomes (1)

• Incidence of otological and systemic adverse events

  Number of AE(Adverse events),SAE(Serious Adverse Events),DLT(Dose Limiting Toxicities)

  26 weeks

Secondary Outcomes (2)

• Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])

  26 weeks

• Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry

  26 weeks

Study Arms (1)

HG205

EXPERIMENTAL

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

Genetic: HG205

Interventions

HG205 GENETIC

The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

HG205

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HuidaGene Therapeutics Co., Ltd.: lead
• Eye & ENT Hospital of Fudan University: collaborator

Study Sites (1)

Eye & ENT Hospital of Fudan University

Shanghai, China

Location

Study Officials

• Study Director

  HuidaGene Therapeutics Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: September 6, 2023
• Study Start: March 30, 2023
• Primary Completion: April 8, 2025
• Study Completion: April 8, 2025
• Last Updated: April 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)