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

An Open-label, Multiple-cohort, Dose-finding, Investigator-initiated Trial to Evaluate the Safety, Tolerability, and Efficacy of HG205 RNA Base-Editing Therapy in Subjects With OTOF-p.Q829X Mutation-associated Hearing Loss

Status

Withdrawn

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06025032

Enrollment

Registered

2023-09-06

Start date

2023-03-30

Completion date

2025-04-08

Last updated

2025-04-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Hearing Loss

Keywords

Congenital hearing loss, OTOF, Q829X, HG205, CRISPR

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.

Interventions

GENETICHG205

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Years to 16 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry	26 weeks	Behavioral audiometry and pure-tone audiometry measurement
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

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026