Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss

Phase 1

Recruiting

• Conditions: Sensorineural Hearing Loss, Bilateral
• Interventions: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

• Registration Number: NCT05821959
• Lead Sponsor: Akouos, Inc.

Brief Summary

Part A of this trial will evaluate the safety and tolerability of a single unilateral administration of one of two dose levels of AAVAnc80-hOTOF and will evaluate the Akouos delivery device to safely achieve the intended product performance.

Detailed Description

The following two dose levels will be tested sequentially:

* 4.1E11 total vg/cochlea

* 8.1E11 total vg/cochlea

Study Timeline

• Study First Submitted: 2023-02-08
• Study First Submitted QC: 2023-04-18
• Study First Posted: 2023-04-20
• Study Start: 2023-09-15
• Status Verified: 2024-10
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Primary Completion: 2028-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1a and Cohort 1b	AAVAnc80-hOTOF via Akouos Delivery Device	Cohort 1a: Two participants aged 7 to 17 years old (inclusive) to receive intracochlear administration of AAVAnc80-hOTOF (dose level 1) in the study ear using a sterile, one-time use investigational medical device Cohort 1b: Up to six eligible participants will be enrolled to receive intracochlear administration of AAVAnc80-hOTOF (dose level 1) in the study ear using a sterile, one-time use investigational medical device; the first three participants will be at least two years of age at the time of AAVAnc80-hOTOF administration and the next three participants may be of any age
Cohort 2	AAVAnc80-hOTOF via Akouos Delivery Device	Cohort 2: Up to six eligible participants will be enrolled to receive intracochlear administration of AAVAnc80-hOTOF (dose level 2) in the study ear using a sterile, one-time use investigational medical device; the first three participants will be at least two years of age at the time of AAVAnc80-hOTOF administration and the next three participants may be of any age

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events (AEs)	through trial completion, approximately 1 year	AEs with relationship to the investigational medicinal product and/or to the administration procedure (including the delivery device)

Secondary Outcome Measures

Name	Time	Method
Auditory Brainstem Response (ABR) Threshold	through trial completion, approximately 1 year	Changes from baseline in ABR intensity threshold (decibels normal hearing level \[dB nHL\])
Performance of the Akouos Delivery Device	through trial completion, approximately 1 year	Performance based on the frequency of device deficiencies observed during delivery of AAVAnc80-hOTOF to the intracochlear space

Trial Locations

Locations (6)

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt Bill Wilkerson Center; 🇺🇸 Nashville, Tennessee, United States

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

University College London; 🇬🇧 London, United Kingdom