Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss

• ClinicalTrials.gov Identifier: NCT05821959
• Recruitment Status: Recruiting
• First Posted: April 20, 2023
• Last Update Posted: February 8, 2024
• Sponsor: Akouos, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Akouos, Inc.

Tracking Information

• First Submitted Date: February 8, 2023
• First Posted Date: April 20, 2023
• Last Update Posted Date: February 8, 2024
• Actual Study Start Date: September 15, 2023
• Estimated Primary Completion Date: October 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2023)

Frequency of Adverse Events (AEs) [ Time Frame: through trial completion, approximately 2 years ]

AEs with relationship to the investigational medicinal product and/or to the administration procedure (including the delivery device)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 18, 2023)

• Auditory Brainstem Response (ABR) Threshold [ Time Frame: through trial completion, approximately 2 years ]
  Changes from baseline in ABR intensity threshold (decibels normal hearing level [dB nHL])
• Performance of the Akouos Delivery Device [ Time Frame: through trial completion, approximately 2 years ]
  Performance based on the frequency of device deficiencies observed during delivery of AAVAnc80-hOTOF to the intracochlear space

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
• Official Title: A Phase 1/2 Trial of AAVAnc80-hOTOF Gene Therapy in Individuals With Sensorineural Hearing Loss Due to Biallelic Otoferlin Gene Mutations
• Brief Summary: Part A of this trial will evaluate the safety and tolerability of a single unilateral administration of one of two dose levels of AAVAnc80-hOTOF and will evaluate the Akouos delivery device to safely achieve the intended product performance.

Detailed Description

The following two dose levels will be tested sequentially:

• 4.1E11 total vg/cochlea
• 8.1E11 total vg/cochlea

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sensorineural Hearing Loss, Bilateral

Intervention

Combination Product: 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.

Study Arms

• Experimental: Cohort 1a and Cohort 1b

  Cohort 1a: 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: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 1) in the study ear using a sterile, one-time use investigational medical device

  Intervention: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device
• Experimental: Cohort 2
  Cohort 2: Participants aged 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration to receive intracochlear administration of AAVAnc80-hOTOF (dose level 2) in the study ear using a sterile, one-time use investigational medical device
  Intervention: Combination Product: AAVAnc80-hOTOF via Akouos Delivery Device

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 18, 2023): 14
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2028
• Estimated Primary Completion Date: October 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age 2 to 17 years old (inclusive) at the time of AAVAnc80-hOTOF administration
2. Biallelic mutations in the otoferlin gene
3. Clinical presentation of Profound 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

Exclusion Criteria:

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. Bilateral cochlear implants
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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Akouos Clinical Trials; +1 (857) 410-1816; clinicaltrials@akouos.com

• Listed Location Countries: Taiwan, United States

Administrative Information

• NCT Number: NCT05821959
• Other Study ID Numbers: AK-OTOF-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Akouos, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Akouos, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Eli Lilly and Company

Investigators

• Study Director: Kathy Reape, MD; Akouos, Inc.

• PRS Account: Akouos, Inc.
• Verification Date: February 2024