Recruiting
Phase 3

Otoferlin Gene Therapy

Sponsor:

Eli Lilly and Company

Code:

NCT05821959

Conditions

Sensorineural Hearing Loss, Bilateral

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

AAVAnc80-hOTOF via Akouos Delivery Device

AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism

Study Details

Brief summary:

Part A of this trial evaluated 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 (LY888891) and evaluated the Akouos Delivery Device, together with the Precision Delivery Mechanism (as applicable), to safely achieve the intended product performance.

Part B of the trial is an open-label, global expansion phase to confirm the efficacy and safety of one dose level of AAVAnc80-hOTOF administered in one or both ear(s). Part B will also evaluate the Intracochlear Delivery System (IDS), which consists of the Akouos Delivery Device, the Precision Delivery Mechanism, and an off-the-shelf syringe.

Part C is a region-specific expansion phase. Part C participants will receive the same dose level of AAVAnc80-hOTOF as participants in Part B, in one or both ear(s) utilizing the IDS.

Part D is a sequential administration phase that allows participants who received AAVAnc80-hOTOF previously in a single ear to receive AAVAnc80-hOTOF administration in the other ear utilizing the IDS.

Conditions

Sensorineural Hearing Loss, Bilateral

Study ID

NCT05821959

Start date

Sep 15, 2023

Status verified date

Sep, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Oct, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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 (Part A) or Severe to Profound (Parts B, C, and D) 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 (with the exception of AK-OTOF-101 for Part D participants)

Study Design

Enrollment

48 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A: Cohort 1a and Cohort 1b

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

experimental: Part A: Cohort 2

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

experimental: Part A: Bilateral Expansion

Bilateral Expansion: up to eight 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).

experimental: Part B

Part B: Sixteen participants of any age will be enrolled to receive a single unilateral or bilateral administration of AAVAnc80-hOTOF. Participants with one CI will receive unilateral administration of AAVAnc80-hOTOF, while participants with no CIs will have the choice to receive a unilateral or bilateral administration of AAVAnc80-hOTOF, provided both ears meet eligibility criteria.

experimental: Part C

Up to ten eligible participants of any age will be enrolled in a region-specific expansion phase to receive a single unilateral or bilateral administration of AAVAnc80-hOTOF. Participants with one CI will receive unilateral administration of AAVAnc80-hOTOF, while participants with no CIs will have the choice to receive a unilateral or bilateral administration of AAVAnc80-hOTOF, provided both ears meet eligibility criteria.

experimental: Part D

Participants of any age may be enrolled into Part D, which is a sequential administration phase that allows participants who received unilateral administration of AAVAnc80-hOTOF in AK-OTOF-101 (Parts A, B, or C) the option to receive dose administration of AAVAnc80-hOTOF in the contralateral ear after completing the Year 1 visit.

Interventions

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.

AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism

AAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time bilateral intracochlear administration using the Akouos Delivery Device together with the Precision Delivery Mechanism.

Primary outcome measure

  • Part A: Frequency of Adverse Events (AEs) [ Time Frame: through trial completion, approximately 1 year ]
  • Co-Primary Parts B, C, and D: ABR Threshold [ Time Frame: through trial completion, approximately 1 year ]
  • Co-Primary Parts B, C, and D: Pure-tone Average [ Time Frame: through trial completion, approximately 1 year ]

Central Contacts and Locations

Central contacts

Lilly Clinical Trials

+1 857-410-1816AkouosClinicalTrials@Lilly.com

Locations

University of California, San Francisco Benioff Children's Hospital

Recruiting

San Francisco, California, United States, 94158

Contacts

Jenny Stephans

415-353-2012Jihyun.Stephans@ucsf.edu

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kesten Anderson

+1 319-356-8320Kesten-Anderson@uiowa.edu

Vanderbilt Bill Wilkerson Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Taha Jan, MD

+1 615-421-1228taha.a.jan@vumc.org

More Information

Sponsor

Eli Lilly and Company

Last update posted

Sep 29, 2026

Last verified

Sep, 2026

Keywords

  • Otoferlin
  • Auditory neuropathy (AN)
  • Deafness, autosomal recessive 9 (DFNB9)
  • Hearing loss
  • Hearing loss, bilateral
  • Hearing loss, sensorineural

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-09-29. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.