Clinical trial NCT06025032: a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Congenital Hearing Loss
Keywords: Congenital hearing loss
OTOF
Q829X
HG205
CRISPR
Lead sponsor: HuidaGene Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Eye & ENT Hospital of Fudan University
First posted: 2023-09-06
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of otological and systemic adverse events
timeFrame: 26 weeks
Secondary outcomes:
measure: Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])
timeFrame: 26 weeks
measure: Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eye & ENT Hospital of Fudan University
Study officials:
affiliation: HuidaGene Therapeutics Co., Ltd.
name: Study Director
role: STUDY_DIRECTOR
References: