Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss

Study Overview
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Brief Summary
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Primary objective of the study is to assess the efficacy of SENS-401 on hearing loss in comparison to placebo at the end of the 4-week treatment period

Detailed Description
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Patients will receive the study drug (SENS-401 or placebo) in the form of tablets by mouth, twice a day (3 tablets in the morning and 3 tablets in the evening), during the first 4 weeks after randomization. SENS-401 is an investigational medicinal product. It belongs to a family of drugs known as 5 HT3 antagonist.

Official Title
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A Two-part, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of SENS-401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss

Conditions
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Severe Sudden Sensorineural Hearing Loss

Intervention / Treatment
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* Drug: SENS-401
* Other: Placebo Oral Tablet
* Drug: SENS-401


Participation Criteria
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Eligibility Criteria
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The main criteria for inclusion: Male or female aged at least 18 years old Patients with unilateral idiopathic sudden sensorineural hearing loss or unilateral/bilateral acute acoustic trauma leading to sudden sensorineural hearing loss. Patients with sudden hearing loss with onset within 96 hours prior to prior to first study drug intake. Patients under highly effective contraception The main criteria for exclusion: Bilateral idiopathic hearing loss Fluctuating hearing loss History of asymmetric hearing (>20 dB difference between ears) to the best knowledge of the patient Severe hearing loss (>90 dB) associated with unilateral (ipsilateral) complete vestibular loss. History of Ménière's disease, autoimmune hearing loss, radiation-induced hearing loss, acoustic neuroma (schwannoma), otosclerosis, suspected perilymph fistula or membrane rupture, suspected retro-cochlear lesion, or barotrauma Previous SSNHL in the affected ear within the past 6 weeks Complete loss of peripheral vestibular function on the affected side Any drug-based therapy for inner ear hearing loss that is ongoing or was performed in the past 6 weeks (except oral corticosteroids) Any ongoing or planned concomitant medication for the treatment of tinnitus until 6 weeks after administration. Any therapy known as ototoxic (e.g. aminoglycosides, cisplatin, loop diuretics, quinine etc.) at the current time or in the past 6 months or planned in the coming 3 months. Acute or chronic otitis media or otitis externa terminated less than 7 days Prior ear surgery of any kind (except ventilating tubes), or cochlear implants Known history of, or concomitant severe hepatic, gastrointestinal, cardiovascular, respiratory, neurological (except vertigo or tinnitus), hematological, renal, dermatological or psychiatric disease or substance abuse Neurological disorders including stroke, demyelinating disease, brain stem or cerebellar dysfunction within the last 3 months. Treatment with any investigational agent within 4 weeks or any past treatment with azasetron or with 5-HT3 antagonists, or any prior or planned treatment by antidepressant treatment containing serotoninergic agents. Patients with either a history of significant arrhythmia, or a history of conditions known to increase the proarrhythmic risk (e.g., congestive heart failure, long QT Syndrome, hypokalemia etc...).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 29 mg dose group<br>Patients will receive the study drug (SENS-401) in the form of tablets by mouth, twice a day, during the first 4 weeks after randomization. | Drug: SENS-401<br>* 29 mg dose group: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks<br>|
| Experimental: 43.5 mg dose group<br>Patients will receive the study drug (SENS-401) in the form of tablets by mouth, twice a day, during the first 4 weeks after randomization. | Drug: SENS-401<br>* 43.5 mg dose groupe: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks<br>|
| Placebo Comparator: placebo oral tablet<br>Patients will receive the study drug (placebo) in the form of tablets by mouth, twice a day, during the first 4 weeks after randomization. | Other: Placebo Oral Tablet<br>* placebo, oral route, by mouth, twice a day, during 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pure Tone Audiometry PTA (dB) (Average of the Hearing Threshold of the 3 Contiguous Most Affected Hearing Frequencies in dB as Identified at Study Entry) From Baseline to the End of Treatment Visit (Day 28 ± 3). | Pure Tone Audiometry PTA (dB) thresholds were determined for each ear at 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for air conduction and 0.5, 1, 2, 3, 4 kHz for bone conduction. Pure Tone Audiometry PTA (dB) is an hearing test used to identify hearing threshold levels of an individual and enabling determination of the degree hearing loss. A clinically significative improvement is defined as a decrease of at least 10 dB of hearing threshold. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Speech Discrimination Threshold From Baseline to Day 28 | The Speech recognition threshold (SRT) (dB) is the minimum hearing level at which an individual can correctly recognize 50% of speech material; the more severe the hearing loss is, the higher SRT is. Spondaic words are the usual and recommended test material for the speech recognition threshold; spondaic words are two-syllable words with equal stress on both syllables (eg, birthday). Per the American Speech-Language-Hearing Association (ASHA) guidelines, subjects were familiarized with the spondaic words prior to the test; they listened to the list of words and indicated if any were unfamiliar. These words could then be eliminated from the list. | Day 28 | 
| Change in Speech Discrimination Threshold From Baseline to Day 84 | The Speech recognition threshold (SRT) (dB) is the minimum hearing level at which an individual can correctly recognize 50% of speech material; the more severe the hearing loss is, the higher SRT is. Spondaic words are the usual and recommended test material for the speech recognition threshold; spondaic words are two-syllable words with equal stress on both syllables (eg, birthday). Per the American Speech-Language-Hearing Association (ASHA) guidelines, subjects were familiarized with the spondaic words prior to the test; they listened to the list of words and indicated if any were unfamiliar. These words could then be eliminated from the list. | Day 84 | 
| Change in Pure Tone Audiometry PTA (dB) (Average of the Hearing Threshold of the 2 Most Affected Hearing Frequencies in dB as Identified at Study Entry) From Baseline to the End of Treatment Visit (Day 28 ± 3). | Pure Tone Audiometry PTA (dB) thresholds were determined for each ear at 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for air conduction and 0.5, 1, 2, 3, 4 kHz for bone conduction. Pure Tone Audiometry PTA (dB) is an hearing test used to identify hearing threshold levels of an individual and enabling determination of the degree hearing loss. A clinically significative improvement is defined as a decrease of at least 10 dB of hearing threshold. | Day 28 | 
| Change in Pure Tone Audiometry PTA (dB) (the Most Affected Hearing Frequencies in dB as Identified at Study Entry) From Baseline to the End of Treatment Visit (Day 28 ± 3). | Pure Tone Audiometry PTA (dB) thresholds were determined for each ear at 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for air conduction and 0.5, 1, 2, 3, 4 kHz for bone conduction. Pure Tone Audiometry PTA (dB) is an hearing test used to identify hearing threshold levels of an individual and enabling determination of the degree hearing loss. A clinically significative improvement is defined as a decrease of at least 10 dB of hearing threshold. | Day 28 | 
| Change in Pure Tone Audiometry PTA (dB) (Average of the Hearing Threshold of the 3 Most Affected Hearing Frequencies in dB as Identified at Study Entry) From Baseline to the End of Study Visit (Day 84 ± 3). | Pure Tone Audiometry PTA (dB) thresholds were determined for each ear at 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz for air conduction and 0.5, 1, 2, 3, 4 kHz for bone conduction. Pure Tone Audiometry PTA (dB) is an hearing test used to identify hearing threshold levels of an individual and enabling determination of the degree hearing loss. A clinically significative improvement is defined as a decrease of at least 10 dB of hearing threshold. | Day 84 |