Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss

Sponsor

Akouos, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05821959

Collaborator

Eli Lilly and Company (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sensorineural Hearing Loss, Bilateral	Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

14 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Trial of AAVAnc80-hOTOF Gene Therapy in Individuals With Sensorineural Hearing Loss Due to Biallelic Otoferlin Gene Mutations

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2028

Anticipated Study Completion Date :

Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1a and Cohort 1b Cohort 1a: 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: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 1) in the study ear using a sterile, one-time use investigational medical device	Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device AAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time unilateral intracochlear administration using the Akouos Delivery Device.
Experimental: Cohort 2 Cohort 2: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 2) in the study ear using a sterile, one-time use investigational medical device	Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device AAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time unilateral intracochlear administration using the Akouos Delivery Device.

Arm

Intervention/Treatment

Experimental: Cohort 1a and Cohort 1b

Cohort 1a: 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: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 1) in the study ear using a sterile, one-time use investigational medical device

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

AAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time unilateral intracochlear administration using the Akouos Delivery Device.

Experimental: Cohort 2

Cohort 2: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 2) in the study ear using a sterile, one-time use investigational medical device

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

AAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time unilateral intracochlear administration using the Akouos Delivery Device.

Outcome Measures

Primary Outcome Measures

Frequency of Adverse Events (AEs) [through trial completion, approximately 2 years]
AEs with relationship to the investigational medicinal product and/or to the administration procedure (including the delivery device)

Secondary Outcome Measures

Auditory Brainstem Response (ABR) Threshold [through trial completion, approximately 2 years]
Changes from baseline in ABR intensity threshold (decibels normal hearing level [dB nHL])
Performance of the Akouos Delivery Device [through trial completion, approximately 2 years]
Performance based on the frequency of device deficiencies observed during delivery of AAVAnc80-hOTOF to the intracochlear space

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 7 to 17 years old (inclusive) for Cohort #1a; age 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration for Cohorts #1b and #2
Biallelic mutations in the otoferlin gene
Clinical presentation of Profound bilateral sensorineural hearing loss as assessed by ABR
Preserved distortion product otoacoustic emissions (DPOAEs)
Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial

Exclusion Criteria:

Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
Bilateral cochlear implants
Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial