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

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).

Study Overview

• Status: Terminated
• Conditions: Hearing Loss, Idiopathic Sudden Sensorineural
• Intervention / Treatment: Other: Placebo; Drug: AM-111 0.4 mg/ml; Drug: AM-111 0.8 mg/ml

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada
    • Penticton, British Columbia, Canada
  • Ontario
    • Markham, Ontario, Canada
• Korea, Republic of
  • Gwangju, Korea, Republic of
  • Pusan, Korea, Republic of
  • Seoul, Korea, Republic of
  • Seoul, Korea, Republic of, 3722
  • Seoul, Korea, Republic of, 61469
  • Seoul, Korea, Republic of, 6591
  • Seoul, Korea, Republic of, 8308
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of
    • Suwon, Gyeonggi, Korea, Republic of
  • Jung-Gu
    • Incheon, Jung-Gu, Korea, Republic of
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0012
  • California
    • Escondido, California, United States, 92025
    • Fresno, California, United States, 93720
    • La Jolla, California, United States, 92037-1214
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Connecticut
    • New Haven, Connecticut, United States, 06519
  • Florida
    • Boca Raton, Florida, United States, 33487
    • Boynton Beach, Florida, United States, 33426-6398
    • Celebration, Florida, United States, 34747
    • Miami, Florida, United States, 33176
    • Miami, Florida, United States, 33133
    • Port Saint Lucie, Florida, United States, 34952
  • Illinois
    • Chicago, Illinois, United States, 60657
  • Iowa
    • Des Moines, Iowa, United States, 50312
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Kentucky
    • Louisville, Kentucky, United States, 40207
  • Michigan
    • Novi, Michigan, United States, 48374
  • Missouri
    • Columbia, Missouri, United States, 65212
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
  • New York
    • Charlotte, New York, United States, 28210
    • New Hyde Park, New York, United States, 11042-1121
    • New Windsor, New York, United States, 12553
    • New York, New York, United States, 10032
    • Rochester, New York, United States, 14618
    • White Plains, New York, United States, 10601-4413
  • North Carolina
    • Matthews, North Carolina, United States, 28105
    • Winston-Salem, North Carolina, United States, 27103-1522
  • Pennsylvania
    • Havertown, Pennsylvania, United States, 19083
    • Philadelphia, Pennsylvania, United States, 19107
  • South Carolina
    • Charleston, South Carolina, United States, 29425
    • Lugoff, South Carolina, United States, 29078
    • Orangeburg, South Carolina, United States, 29118
  • Tennessee
    • Nashville, Tennessee, United States, 37232-8605
  • Texas
    • Fort Sam Houston, Texas, United States, 78234
  • Utah
    • Saint George, Utah, United States, 84790
    • Salt Lake City, Utah, United States, 84102
  • Virginia
    • Norfolk, Virginia, United States, 23507
  • Washington
    • Tacoma, Washington, United States, 98431-1100

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Auris Medical, Inc.
• Investigators: Study Director: Thomas Meier, Auris Medical, Inc.

Publications and helpful links

Helpful Links

• Study webpage with information on study and sites participating

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): August 7, 2020
• Last Update Submitted That Met QC Criteria: July 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Hearing Loss; Neurologic Manifestations; Signs and Symptoms; Deafness; Hearing Loss, Sensorineural; Ear Diseases; Hearing Disorders; Otorhinolaryngologic Diseases; Sensation Disorders; Hearing Loss, Unilateral; Hearing and Speech Impairment
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural
• Other Study ID Numbers: AM-111-CL-15-01