Brief Summary
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).
Brief Title
Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment
Detailed Description
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hearing Loss, Idiopathic Sudden Sensorineural
Eligibility Criteria
Inclusion Criteria:
1. Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) with onset within 72 hours prior to study treatment;
2. 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);
3. 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;
4. Age ≥ 18 years on the day of screening;
Exclusion Criteria:
1. Bilateral ISSNHL;
2. Acute hearing loss from noise trauma, barotrauma or head trauma;
3. 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;
4. History of autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops or Menière's disease in either ear;
5. History of chronic inflammatory or suppurative ear disease or cholesteatoma in the affected ear;
6. Current evidence or history of acoustic neuroma or other retrocochlear damage in the affected ear;
7. History of otosclerosis in the affected ear;
8. Suspected perilymph fistula or membrane rupture in the affected ear;
9. Congenital hearing loss;
10. History of ISSNHL in the past 2 years;
11. Otitis media or otitis externa that is ongoing or ended within 7 days prior to study treatment;
1. Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) with onset within 72 hours prior to study treatment;
2. 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);
3. 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;
4. Age ≥ 18 years on the day of screening;
Exclusion Criteria:
1. Bilateral ISSNHL;
2. Acute hearing loss from noise trauma, barotrauma or head trauma;
3. 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;
4. History of autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops or Menière's disease in either ear;
5. History of chronic inflammatory or suppurative ear disease or cholesteatoma in the affected ear;
6. Current evidence or history of acoustic neuroma or other retrocochlear damage in the affected ear;
7. History of otosclerosis in the affected ear;
8. Suspected perilymph fistula or membrane rupture in the affected ear;
9. Congenital hearing loss;
10. History of ISSNHL in the past 2 years;
11. Otitis media or otitis externa that is ongoing or ended within 7 days prior to study treatment;
Inclusion Criteria
Inclusion Criteria:
1. Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) with onset within 72 hours prior to study treatment;
2. 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);
3. 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;
4. Age ≥ 18 years on the day of screening;
1. Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) with onset within 72 hours prior to study treatment;
2. 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);
3. 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;
4. Age ≥ 18 years on the day of screening;
Gender
All
Gender Based
false
Keywords
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02809118
Org Class
Industry
Org Full Name
Auris Medical, Inc.
Org Study Id
AM-111-CL-15-01
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment
Primary Outcomes
Outcome Description
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.
Outcome Measure
Pure Tone Average (PTA)
Outcome Time Frame
Day 0 and Day 91: The study was prematurely terminated.
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 0 and Day 91: The study was prematurely terminated.
Outcome Measure
Word Recognition Score (WRS) - Main Secondary
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Elizabeth Dinces
Investigator Email
edinces@montefiore.org
Investigator Phone
718-920-8417