Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
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.
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)
COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device, COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
Sensorineural Hearing Loss, Bilateral
Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural