AM-111 in the Treatment of Acute Inner Ear Hearing Loss

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to test the effectiveness and safety of the study drug, AM-111. AM-111 is tested for the treatment of sudden sensorineural hearing loss where the cause is unknown.

Detailed Description
-----------------
This phase III study is assessing the drug's safety and is aiming to demonstrate efficacy of intratympanic AM-111 injections in the treatment of severe to profound idiopathic sudden sensorineural hearing loss (ISSNHL). The active pharmaceutical ingredient of AM-111 is the 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.

Official Title
-----------------
Efficacy and Safety of AM-111 in the Treatment of Acute Inner Ear Hearing Loss

Conditions
-----------------
Hearing Loss

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Unilateral ISSNHL with onset within 72 hours prior to study treatment; Mean hearing threshold of equal to or worse than (≥) 60 dB averaged across the 3 most affected contiguous air conduction audiometric pure tone frequencies (pure tone average, PTA);* Mean hearing loss of equal to or worse than (≥) 40 dB averaged across the air conducted PTA frequencies compared with the unaffected contralateral ear or reference values from a pre-existing audiogram or ISO 7029;2000 norm values in case of asymmetric hearing prior to the ISSNHL incident; Age ≥ 18 and ≤ 65 years on the day of screening; Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Bilateral ISSNHL; Acute hearing loss from noise trauma, barotrauma or head trauma; History of autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops or Menière's disease in the affected ear; History of chronic inflammatory or suppurative ear disease or cholesteatoma in the affected ear; 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; Other protocol-defined exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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> <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> <br> |
| 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> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pure tone average (PTA; average of the hearing threshold of three contiguous most affected hearing frequencies in dB) | Assessment with pure tone audiometry/ Measurement at 8 frequencies/ Final outcome is the absolute improvement in PTA from D0 to D28 | Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Deafness, Hearing Loss, Sensorineural, Ear Diseases, Hearing Disorders, Otorhinolaryngologic Diseases, Sensation Disorders, Signs and Symptoms, Hearing and Speech impairment, Hearing Loss, Unilateral