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

Congenital Hearing Loss Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06025032
• Other study ID #: HG20501
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: November 30, 2024
• Est. completion date: April 28, 2030

Study information

• Verified date: November 2023
• Source: HuidaGene Therapeutics Co., Ltd.
• Contact: Study Director
• Phone: +86 021-25076143
• Email: HG20501[@]huidagene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: April 28, 2030
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Congenital Hearing Loss
• Deafness
• Hearing Loss

Intervention

Genetic:
• HG205
The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

Locations

Country	Name	City	State
China	Eye & ENT Hospital of Fudan University	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
HuidaGene Therapeutics Co., Ltd.	Eye & ENT Hospital of Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of otological and systemic adverse events	Number of AE(Adverse events),SAE(Serious Adverse Events),DLT(Dose Limiting Toxicities)	26 weeks
Secondary	Change from baseline in ABR(Auditory Brainstem Response) intensity threshold (decibels normal hearing level [dB nHL])	ABR intensity threshold (decibels normal hearing level [dB nHL]) measurement	26 weeks
Secondary	Change from baseline in hearing performance by behavioral audiometry with pure-tone audiometry	Behavioral audiometry and pure-tone audiometry measurement	26 weeks