Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment

Study Overview
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Brief Summary
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The primary objective of the trial is the confirmation of the efficacy of AM-111 in the recovery of severe to profound idiopathic sudden sensorineural hearing loss (ISSNHL).

Detailed Description
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This is a Phase III, randomized, double-blind, placebo-controlled, parallel group, multi-center, efficacy and safety trial of AM-111 in the treatment of subjects suffering from severe to profound idiopathic sudden sensorineural hearing loss. The active pharmaceutical ingredient of AM-111 is a JNK inhibitor (D-JNKI-1), a synthetic peptide consisting of 31 D-amino acids, which acts as a c-Jun N-terminal kinase (JNK) ligand. The study consists of one treatment visit and a follow-up period until day 91. Study participants will receive, after topical anesthesia of the tympanic membrane, AM-111 0.4 mg/mL or 0.8 mg/mL or placebo, administered into the affected ear. Following the administration, subjects will rest in a supine or reclined position for 30 minutes. Study participants will have the option for a course of oral corticosteroids.

Official Title
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Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment

Conditions
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Hearing Loss, Idiopathic Sudden Sensorineural

Intervention / Treatment
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* Drug: AM-111 0.4 mg/ml
* Drug: AM-111 0.8 mg/ml
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) with onset within 72 hours prior to study treatment; Mean hearing threshold of equal to or worse than (≥) 60 dB averaged across those 3 contiguous air conduction audiometric pure tone frequencies that show the highest mean hearing loss compared with the unaffected contralateral ear or, in case of history of asymmetric hearing, corresponding values from a pre-existing audiogram for the affected ear not older than 2 years prior to the ISSNHL incident (defined as pure tone average, PTA); Mean hearing loss of equal to or worse than (≥) 40 dB averaged across the air conduction thresholds at the pure tone average frequencies compared with the unaffected contralateral ear or, in case of history of asymmetric hearing, corresponding values from a preexisting audiogram for the affected ear not older than 2 years prior to the ISSNHL incident; Age ≥ 18 years on the day of screening; Exclusion Criteria: Bilateral ISSNHL; Acute hearing loss from noise trauma, barotrauma or head trauma; Air-bone gap greater than 20 dB at the average of 3 contiguous test frequencies below 4 kHz, when the air-bone gap is measurable; History of autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops or Menière's disease in either ear; History of chronic inflammatory or suppurative ear disease or cholesteatoma in the affected ear; Current evidence or history of acoustic neuroma or other retrocochlear damage in the affected ear; History of otosclerosis in the affected ear; Suspected perilymph fistula or membrane rupture in the affected ear; Congenital hearing loss; History of ISSNHL in the past 2 years; Otitis media or otitis externa that is ongoing or ended within 7 days prior to study treatment;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo gel for intratympanic use | Other: Placebo<br>* Placebo gel is administered with a single dose into the affected ear after topical anesthesia<br>|
| Experimental: AM-111 0.4 mg/ml<br>AM-111 gel for intratympanic use (0.4 mg/ml AM-111) | Drug: AM-111 0.4 mg/ml<br>* AM-111 0.4 mg/mL gel is administered with a single dose into the affected ear after topical anesthesia<br>* Other names: Brimapitide;|
| Experimental: AM-111 0.8 mg/ml<br>AM-111 gel for intratympanic use (0.8 mg/ml AM-111) | Drug: AM-111 0.8 mg/ml<br>* AM-111 0.8 mg/mL gel is administered with a single dose into the affected ear after topical anesthesia<br>* Other names: Brimapitide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pure Tone Average (PTA) | Measurement of the recovery of hearing between Day 0 (before treatment) and Day 91, i.e. change in pure tone audiometry between Day 0 and Day 91. The study was prematurely terminated. It was pre-specified not to complete analyses due to premature termination. Not all data planned were collected. No meaningful efficacy analysis could be performed on the data. | Day 0 and Day 91: The study was prematurely terminated. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Word Recognition Score (WRS) - Main Secondary | Change in WRS from Day 0 to Day 91. The WRS was determined with country-/language-specific word lists. At least 20 mono- or disyllabic words were presented in random order. After each word was presented to the subject, the subject was asked to repeat it, and to guess it, if he/she was not sure of the word. The study was prematurely terminated. It was pre-specified not to complete analyses due to premature termination. Not all data planned were collected. No meaningful efficacy analysis could be performed on the data. | Day 0 and Day 91: The study was prematurely terminated. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deafness, Hearing Loss, Hearing Loss, Sensorineural, Ear Diseases, Hearing Disorders, Nervous System Diseases, Neurologic Manifestations, Otorhinolaryngologic Diseases, Sensation Disorders, Signs and Symptoms, Hearing and Speech Impairment, Hearing Loss, Unilateral