Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss

a study on Hearing Loss Sensorineural Hearing Loss Neuropathy

Summary

Location
at San Francisco, California and other locations
Dates
study started
study ends around

Description

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.

Official Title

A Trial of AAVAnc80-hOTOF Gene Therapy in Individuals With Sensorineural Hearing Loss Due to Otoferlin Gene Mutations

Details

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

Keywords

Sensorineural Hearing Loss, Bilateral, Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural, Sensorineural Hearing Loss, Autosomal Recessive 9 Deafness, Auditory neuropathy, Deafness, Bilateral Hearing Loss, AAVAnc80-hOTOF via Akouos Delivery Device, AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism, Bilateral Expansion

Eligibility

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)

Locations

  • UCSF Benioff Children's Hospital accepting new patients
    San Francisco California 94158 United States
  • University of Iowa accepting new patients
    Iowa City Iowa 52242 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Eli Lilly and Company
ID
NCT05821959
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 48 study participants
Last Updated
Contact us about this trial