Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorEli Lilly and Company
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
None
Trial design
Design model
Sequential
Treatments tested in this trial
AAVAnc80-hOTOF via Akouos Delivery Device
Combination productAAVAnc80-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
Combination productAAVAnc80-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.
Treatment groups
48 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Part A: Cohort 1a and Cohort 1bExperimental treatment 1 intervention
Group B: Part A: Cohort 2Experimental treatment 1 intervention
Group C: Part A: Bilateral ExpansionExperimental treatment 1 intervention
Group D: Part BExperimental treatment 1 intervention
Group E: Part CExperimental treatment 1 intervention
Group F: Part DExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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)
Time frame
through trial completion, approximately 1 year2
Co-Primary Parts B, C, and D: ABR Threshold
Changes from baseline in ABR intensity threshold (decibels normal hearing level \[dB nHL\]
Time frame
through trial completion, approximately 1 year3
Co-Primary Parts B, C, and D: Pure-tone Average
Changes from baseline in the average of behavioral pure-tone audiometry thresholds
Time frame
through trial completion, approximately 1 yearSecondary outcomes
1
Part A: Auditory Brainstem Response (ABR) Threshold
Changes from baseline in ABR intensity threshold (decibels normal hearing level \[dB nHL\])
Time frame
through trial completion, approximately 1 year2
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
Time frame
through trial completion, approximately 1 year3
Parts B, C, and D: Auditory Skills Checklist (ASC)
Change from Baseline for ASC total score
Time frame
through trial completion, approximately 1 yearOther outcomes
1
Parts B, C, and D: Performance of the Intracochlear Delivery System to deliver AAVAnc80-hOTOF to the intracochlear space
Performance based on the frequency of device deficiencies observed during delivery of AAVAnc80-hOTOF to the intracochlear space
Time frame
through trial completion, approximately 1 yearSponsors and contacts
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Source ClinicalTrials.gov