Idiopathic sudden sensorineural hearing loss MedDRA version: 19.1 Level: PT Classification code 10043882 Term: Tinnitus System Organ Class: 10013993 - Ear and labyrinth disorders
Conditions
Interventions
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
Conc
Sponsors
Auris Medical AG
Eligibility
Sex/Gender
All
Inclusion 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
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ;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. ;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Bulgaria, Czech Republic, Germany, Hungary, Poland, Russian Federation, Serbia, Spain, Taiwan, Thailand, Turkey
Contacts
Public ContactTomas Meyer
Auris Medical Ltd.
Outcome results
None listed