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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Congenital Hearing Loss
• Intervention / Treatment: Genetic: HG205

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: +86 021-25076143; Email: HG20501@huidagene.com

Study Locations

• China
  • Shanghai, China
    • Eye & ENT Hospital of Fudan University
    • Contact: Yilai Shu, MD,PhD; Phone Number: +86 021-64377134
    • Principal Investigator: Yilai Shu, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Genetic: HG205; The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: HuidaGene Therapeutics Co., Ltd.
• Collaborators: Eye & ENT Hospital of Fudan University
• Investigators: Study Director: Study Director, HuidaGene Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): April 28, 2030

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: CRISPR; OTOF; Congenital hearing loss; Q829X; HG205
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: HG20501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No