Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss

Akouos

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Sensorineural Hearing Loss, Bilateral

Treatments: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Study type: Interventional

Funder types: Industry

Identifiers

NCT05821959

AK-OTOF-101

Details and patient eligibility

About

Part A of this trial will evaluate the safety and tolerability of a single surgical administration procedure in one or both ear(s) with one of two dose levels of AAVAnc80-hOTOF and will evaluate the Akouos Delivery Device to safely achieve the intended product performance.

Full description

The following two dose levels will be tested:

• Up to 4.1E11 total vg/cochlea
• Up to 8.1E11 total vg/cochlea

Enrollment: 18 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Criteria for Inclusion:

1. Participants may be of any age, based on Cohort Criteria
2. At least two mutations in the otoferlin gene
3. Clinical presentation of Profound bilateral sensorineural hearing loss as assessed by ABR
4. Preserved distortion product otoacoustic emissions (DPOAEs)
5. 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

Criteria for Exclusion:

1. 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
2. Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
3. 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Cohort 1a and Cohort 1b

Experimental group

Description:

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

Treatment:

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Cohort 2

Experimental group

Description:

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

Treatment:

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Bilateral Expansion

Experimental group

Description:

Bilateral Expansion: up to four eligible participants of any age, and no cochlear implants, may be eligible for enrollment into the Bilateral Expansion Cohort (simultaneous bilateral administration of AAVAnc80-hOTOF).

Treatment:

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device