A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations (AUDIOGENE)

A Phase I/II, Open-ended, Adaptative, Open Label Dose Escalation and Expansion Clinical Trial to Evaluate the Efficacy and Safety of Unilateral Intracochlear Injection of SENS-501 Using an Injection System in Children with Severe to Profound Hearing Loss Due to Otoferlin Gene Mutations

This study intends to assess safety, tolerability, and efficacy of SENS-501 in children between the ages of 6-31 months with pre-lingual hearing loss due to a mutation in the Otoferlin gene.

Study Overview

• Status: Recruiting
• Conditions: Otorhinolaryngologic Diseases; Ear Diseases; Hearing Disorders; Deafness; Hearing Loss, Sensorineural; Congenital Deafness; DFNB9; OTOF Gene Mutation
• Intervention / Treatment: Combination product: SENS-501 administration

Detailed Description

It is a multicenter, adaptive open-label, non-randomized, dose-escalation, and expansion study to assess safety, tolerability, and efficacy following intracochlear administration of SENS-501.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Géraldine HONNET, MD; Email: geraldine.honnet@sensorion-pharma.com
• Study Contact Backup: Name: Lionel HOVSEPIAN, MD; Phone Number: +33 7 86 31 13 76; Email: lionel.hovsepian@sensorion-pharma.com

Study Locations

• Australia
  • Westmead, Australia, NSW 2145
    • Recruiting
    • Childrens Hospital Westmead
    • Contact: Clinical Research Coordinator/Nurse; Phone Number: +61 2 7825 3048; Email: SCHN-CHW-CRC@health.nsw.gov.au
    • Contact: Catherine Birman, Pr
• France
  • Paris, France, 75015
    • Recruiting
    • Hôpital Necker Enfants Malades
    • Contact: Natalie LOUNDON, Pr; Phone Number: +33(0)171396782; Email: secretariat.loundon@nck.aphp.fr
    • Contact: Natalie LOUNDON, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children (male or female) ≥ 6 to ≤ 31 months at the time of inclusion
• Severe to profound hearing loss assessed by auditory brainstem response (ABR)
• Biallelic mutation in the Otoferlin gene
• Presence of Otoacoustic emissions (OAEs)
• Documented normal cochlea and internal auditory canals
• Patients with intact vestibular function

Exclusion Criteria:

• History of chronic, acute, or major disease, or unspecified reasons, that in the opinion of the Investigator, makes the participant unsuitable for participation in the study or constitutes an unacceptable risk.
• Have been dosed in a previous gene therapy clinical trial
• Patients with a prior or current cochlear implant
• Any contraindication to the surgery determined by the surgeon or anesthesia determined by the anesthesiologist, or designee, or history of therapy known as ototoxic (e.g., cisplatin, high dose and long treatment with aminoglycosides, etc.) for an extended period (more than 2 weeks).
• Participation in any other interventional clinical trial
• Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the participant or would preclude the participant from successful completion of the study or might interfere with the evaluation of study treatment
• Anticipated noncompliance with the protocol requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation - Low dose group; Intracochlear administration of a Low dose of SENS-501 in one ear, with a dedicated administration system	Combination product: SENS-501 administration; Administration of SENS-501 with a dedicated administration system
Experimental: Dose escalation - High dose group; Intracochlear administration of a High dose of SENS-501 in one ear, with a dedicated administration system	Combination product: SENS-501 administration; Administration of SENS-501 with a dedicated administration system
Experimental: Dose expansion group; Intracochlear administration of SENS-501 in one ear, with a dedicated administration system, at the dose recommended following the Dose escalation phase	Combination product: SENS-501 administration; Administration of SENS-501 with a dedicated administration system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of SENS-501	Number of study-related adverse events (AEs) and serious adverse events (SAEs).	5 years
Efficacy of SENS-501 assessed by ABR	Improvement of hearing threshold measured by auditory brainstem response (ABR)	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of SENS-501	Number of study-related adverse events (AEs) and serious adverse events (SAEs).	5 years
Efficacy of SENS-501 assessed by ABR	Improvement of hearing threshold measured by auditory brainstem response (ABR)	5 years
Clinical performance of the administration system	Administration success ; Users' feedback questionnaire on the administration and use of the devices	1 day
Safety of the administration system	Adverse device effects and Device deficiencies, Procedure complications	5 years
Usability of the administration system	Usability questionnaire	1 day
Efficacy of SENS-501 assessed by PTA	Improvement of hearing threshold measured by Pure-tone audiometry (PTA)	5 years

Collaborators and Investigators

• Sponsor: Sensorion
• Investigators: Study Chair: Natalie LOUNDON, Pr, Hôpital Necker Enfants Malades

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): September 26, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Hearing Loss; Gene therapy; Cochlear implant; Hearing impairment; Deafness; DFNB9; Hearing disorder; OTOF Gene Mutation; otoferlin; AUDIOGENE; SENS-501; Congenital Hearing loss
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases
• Other Study ID Numbers: SENS-501-101; 2023-504466-28-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No