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

• Register: EUCTR
• Last refreshed on: 30 October 2017
• Main ID: EUCTR2013-002077-21-BG
• Date of registration: 04/09/2015
• Prospective Registration: Yes
• Primary sponsor: Auris Medical AG
• Public title: Efficacy and Safety of AM-111 in the Treatment of Acute Inner Ear Hearing Loss
• Scientific title: Efficacy and Safety of AM-111 in the Treatment of Acute Inner Ear Hearing Loss - HEALOS
• Date of first enrolment: 15/10/2015
• Target sample size: 255
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002077-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary, Poland, Russian Federation, Serbia, Spain, Taiwan, Thailand, Turkey

Contacts

• Name: Tomas Meyer
• Affiliation: Auris Medical Ltd.

• Name: Tomas Meyer
• Affiliation: Auris Medical Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Unilateral ISSNHL with onset within 72 hours prior to study treatment;
2. 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);*
3. 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;*
4. Age = 18 and = 65 years on the day of screening;
5. Negative urine pregnancy test for women of childbearing potential. Women are not considered to be of childbearing potential if they meet one of the following criteria:
- They have had a hysterectomy or tubal ligation at least one cycle prior to signing the Informed Consent Form (ICF) or
- They are post-menopausal, with at least one year since their last menstrual period;
6. Willing and able to attend the trial visits;
7. Able to read and understand trial documents and follow Investigator instructions;
8. Able to understand and follow trial personnel instructions during audiologic measurements;
9. Willing and able to use adequate hearing protection and to refrain from engaging in activities or work involving loud noise exposure where sufficient hearing protection is not possible or ensured;
10. Willing and able to protect the ear canal and middle ear from water exposure for as long as the tympanic membrane is not fully closed;
11. Signed Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved ICF.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Bilateral ISSNHL;
2. Acute hearing loss from noise trauma, barotrauma or head trauma;
3. History of autoimmune hearing loss, radiation-induced hearing loss, endolymphatic hydrops or Menière’s disease in the affected ear;
4. History of chronic inflammatory or suppurative ear disease or cholesteatoma in the affected ear;
5. History of acoustic neuroma or other retrocochlear damage in the affected ear;
6. History of otosclerosis in the affected ear;
7. Suspected perilymph fistula or membrane rupture in the affected ear;
8. Congenital hearing loss;
9. History of ISSNHL in the past 2 years;
10. Otitis media or otitis externa that is ongoing or ended within 7 days prior to study treatment;
11. Radiation therapy in the head and neck area within the past 5 years;
12. Abnormality of the tympanic membrane in the affected ear that would preclude i.t. administration;
13. Any pre-treatment within two weeks prior to enrolment, ongoing treatment or planned treatment of ISSNHL-related hearing loss or tinnitus including pharmacological medication or non-pharmacological treatment (other than prednisolone or prednisone reserve therapy following FUV2);
14. Any therapy known as ototoxic (e.g. aminoglycosides, cisplatin, loop diuretics, quinine etc.) in the 3 months prior to trial inclusion;
15. History within the past 2 years or presence of drug abuse or alcoholism;
16. Subjects with diagnosed anxiety disorders, depression, schizophrenia or other significant psychiatric diseases requiring current drug treatment or subjects who required treatment in the previous 3 months prior to enrolment for any of these diseases;
17. Any clinically relevant respiratory, cardiovascular, neurological disorder (except vertigo or tinnitus) or other abnormality that in the opinion of the Investigator or Sponsor may pose a safety risk to a subject in this study, which may confound efficacy or safety assessment, or may interfere with study participation;
18. Known or suspected ongoing active infection of HIV, hepatitis C or B, or herpes zoster;
19. Women who are breast-feeding, pregnant or who are planning to become pregnant during the study;
20. Women of childbearing potential who are unwilling or unable to use an effective method of avoiding pregnancy from the screening visit until the end of the study (FUV4). Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of less than 1 used consistently and correctly (including implantable, injectable, oral and transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap, or a sterile sexual partner, or being abstinent);
21. Concurrent participation in another clinical study or participation in another clinical study within 30 days prior to randomisation (TV).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]

Idiopathic sudden sensorineural hearing loss
MedDRA version: 19.1 Level: PT Classification code 10043882 Term: Tinnitus System Organ Class: 10013993 - Ear and labyrinth disorders

Intervention(s)

Product Name: AM-111
Product Code: AM-111
Pharmaceutical Form: Gel for injection
INN or Proposed INN: AM-111
CAS Number: 1624290-55-6
Current Sponsor code: D-JNKI-1
Other descriptive name: XG-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.4 -
Pharmaceutical form of the placebo: Gel for injection
Route of administration of the placebo: Intratympanic use (Noncurrent)

Product Name: AM-111
Product Code: AM-111
Pharmaceutical Form: Gel for injection
INN or Proposed INN: AM-111
Current Sponsor code: D-JNKI-1
Other descriptive name: XG-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.8-
Pharmaceutical form of the placebo: Gel for injection
Route of administration of the placebo: Intratympanic use (Noncurrent)

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 28

Primary end point(s): Primary efficacy endpoint:
Absolute improvement in PTA from baseline to FUV3.

Primary safety endpoint:
Occurrence of clinically relevant hearing deterioration (defined as increase in air conduction hearing threshold = 10 dB at the average of any two contiguous test frequencies) from baseline to FUV3 in the treated ear. The analysis will be conducted also with bone conduction hearing threshold values.

Main Objective: Confirmation of the efficacy of AM-111 in the recovery of severe to profound idiopathic sudden sensorineural hearing loss (ISSNHL).

Secondary Objective: • Further evaluation of the dose response relationship for AM-111 in the recovery of ISSNHL;
• Assessment of the efficacy of AM-111 in achieving complete remission of ISSNHL-related tinnitus;
• Assessment of safety and local tolerance of AM-111.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints:
• Absolute improvement in PTA from baseline to FUV1, FUV2 and FUV4 ;
• Proportion of subjects receiving corticosteroid reserve therapy;
• Frequency of complete hearing recovery at FUV3 and FUV4;
• Frequency of complete tinnitus remission at FUV4 in subjects with ISSNHL-related tinnitus at baseline.

Secondary safety endpoints
• Occurrence of clinically relevant hearing deterioration from baseline to all FUVs (other than FUV3) (air conduction) in the treated ear;
• Difference in occurrence of clinically relevant hearing deterioration from baseline to all FUVs between treated and untreated contralateral ear;
• Occurrence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), differentiated by causal relationship to:
- The IMP;
- The intratympanic IMP administration;
- Other trial procedures; or
- Other reasons not related to the trial.

Timepoint(s) of evaluation of this end point: Day 14, Day 28, Day 91

Secondary ID(s)

AM-111-CL-13-01

Source(s) of Monetary Support

Auris Medical AG