Sensorineural Hearing Loss, BilateralPhase 3NCT05821959
Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
A Phase 3 study testing AAVAnc80-hOTOF via Akouos Delivery Device and AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism in people with Sensorineural Hearing Loss, Bilateral, run by Eli Lilly and Company at 9 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Sensorineural Hearing Loss, Bilateral
- What is being tested?
- AAVAnc80-hOTOF via Akouos Delivery Device and AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 15 Sep 2023to Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Criteria for Inclusion:
- Participants may be of any age, based on Cohort Criteria
- At least two mutations in the otoferlin gene
- Clinical presentation of Profound (Part A) or Severe to Profound (Parts B, C, and D) 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
Criteria for Exclusion:
- 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
- Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
- 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)
Trial locations and contacts
9 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 4 countries
United States6 sites, 3 recruiting
- Active, not recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
- Active, not recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Kesten Anderson, +1 319-356-8320, Kesten-Anderson@uiowa.edu
- Recruiting
Vanderbilt Bill Wilkerson Center
Nashville, Tennessee, 37232
Taha Jan, MD, +1 615-421-1228, taha.a.jan@vumc.org
- Active, not recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19146
- Recruiting
University of California, San Francisco Benioff Children's Hospital
San Francisco, California, 94158
Jenny Stephans, 415-353-2012, Jihyun.Stephans@ucsf.edu
Canada1 site
- Active, not recruiting
The Hospital for Sick Children Jaina.negandhi@sickkids.ca +1 (416) 813 6683
Toronto, Ontario, M5G 1X8
Taiwan1 site
- Active, not recruiting
National Taiwan University Hospital
Taipei, 100
United Kingdom1 site
- Active, not recruiting
University College London
London, United Kingdom, NW1 2PG
About this study
Official title: A Trial of AAVAnc80-hOTOF Gene Therapy in Individuals With Sensorineural Hearing Loss Due to Otoferlin Gene Mutations
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.
Read more
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.
Read the detailed description
The following two dose levels were tested in Part A:
- Up to 4.1E11 total vg/cochlea
- Up to 8.1E11 total vg/cochlea
The following dose level will be tested in Part B, C, and D:
- 8.1E11 total vg/cochlea
- Conditions
- Sensorineural Hearing Loss, Bilateral
- Being tested
- AAVAnc80-hOTOF via Akouos Delivery Device, AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
- Keywords
- Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural
- Medical subject headings
- Hearing Loss, Sensorineural, Deafness, Autosomal Recessive 9, Auditory neuropathy, Deafness, Hearing Loss, Hearing Loss, Bilateral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAVAnc80-hOTOF via Akouos Delivery DeviceCombination product
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 MechanismCombination product
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort 1a and Cohort 1b | Experimental | 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 Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device |
| Part A: Cohort 2 | Experimental | 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 Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device |
| Part A: Bilateral Expansion | Experimental | 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). Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism |
| Part B | Experimental | 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. Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism |
| Part C | Experimental | 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. Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism |
| Part D | Experimental | 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. Receives: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Frequency of Adverse Events (AEs)
AEs with relationship to the investigational medicinal product and/or to the administration procedure (including the delivery system)
Measured: through trial completion, approximately 1 year
Co-Primary Parts B, C, and D: ABR Threshold
Changes from baseline in ABR intensity threshold (decibels normal hearing level [dB nHL]
Measured: through trial completion, approximately 1 year
Co-Primary Parts B, C, and D: Pure-tone Average
Changes from baseline in the average of behavioral pure-tone audiometry thresholds
Measured: through trial completion, approximately 1 year
Secondary outcomes (3)
Part A: Auditory Brainstem Response (ABR) Threshold
Changes from baseline in ABR intensity threshold (decibels normal hearing level [dB nHL])
Measured: through trial completion, approximately 1 year
Part A: Performance of the Akouos Delivery Device and Precision Delivery Mechanism
Performance based on the frequency of device deficiencies observed during delivery of AAVAnc80-hOTOF to the intracochlear space
Measured: through trial completion, approximately 1 year
Parts B, C, and D: Auditory Skills Checklist (ASC)
Change from Baseline for ASC total score
Measured: through trial completion, approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2023
- Study start15 Sep 2023
- Primary completionOct 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sensorineural Hearing Loss, BilateralStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sarah Neuhaus, D.O., Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05821959
- Sponsor's protocol ID
- AK-OTOF-101
- Other IDs
- 2026-525943-33-00, J8E-MC-OVAA
- Status last verified
- Sep 2026
- First submitted
- 8 Feb 2023
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of AAVAnc80-hOTOF Gene Therapy in Individuals With Sensorineural Hearing Loss Due to Otoferlin Gene Mutations
- ClinicalTrials.gov ID
- NCT05821959
- Acronym / sponsor ID
- AK-OTOF-101
- Conditions
- Sensorineural Hearing Loss, Bilateral
- Keywords
- Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 15 Sep 2023 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 20 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The following two dose levels were tested in Part A:
- Up to 4.1E11 total vg/cochlea
- Up to 8.1E11 total vg/cochlea
The following dose level will be tested in Part B, C, and D:
- 8.1E11 total vg/cochlea
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A: Cohort 1a and Cohort 1b | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery DeviceCohort 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 |
| Part A: Cohort 2 | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery DeviceCohort 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 |
| Part A: Bilateral Expansion | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery MechanismBilateral 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). |
| Part B | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery MechanismPart 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. |
| Part C | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery MechanismUp 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. |
| Part D | Experimental | Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery MechanismParticipants 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAVAnc80-hOTOF via Akouos Delivery DeviceAAVAnc80-hOTOF is a sterile suspension intended to be administered via a one-time unilateral intracochlear administration using the Akouos Delivery Device. | Combination product | Part A: Cohort 1a and Cohort 1b, Part A: Cohort 2 |
| AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery MechanismAAVAnc80-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. | Combination product | Part A: Bilateral Expansion, Part B, Part C, Part D |
Primary outcome
Part A: Frequency of Adverse Events (AEs)
Time frame: through trial completion, approximately 1 year
AEs with relationship to the investigational medicinal product and/or to the administration procedure (including the delivery system)
Co-Primary Parts B, C, and D: ABR Threshold
Time frame: through trial completion, approximately 1 year
Changes from baseline in ABR intensity threshold (decibels normal hearing level [dB nHL]
Co-Primary Parts B, C, and D: Pure-tone Average
Time frame: through trial completion, approximately 1 year
Changes from baseline in the average of behavioral pure-tone audiometry thresholds
3 secondary outcomes
Part A: Auditory Brainstem Response (ABR) Threshold
Time frame: through trial completion, approximately 1 year
Part A: Performance of the Akouos Delivery Device and Precision Delivery Mechanism
Time frame: through trial completion, approximately 1 year
Parts B, C, and D: Auditory Skills Checklist (ASC)
Time frame: through trial completion, approximately 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sarah Neuhaus, D.O. study director
Eli Lilly and Company
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AAVAnc80-hOTOF via Akouos Delivery Device and AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism in people with Sensorineural Hearing Loss, Bilateral, run by Eli Lilly and Company at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada, Taiwan, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lilly Clinical Trials (+1 857-410-1816, AkouosClinicalTrials@Lilly.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Frequency of Adverse Events (AEs) (time frame: through trial completion, approximately 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.