Severe Sudden Sensorineural Hearing Loss
Conditions
Brief summary
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
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.
Interventions
DRUGSENS-401
29 mg dose group: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks
OTHERPlacebo Oral Tablet
placebo, oral route, by mouth, twice a day, during 4 weeks
Sponsors
Sensorion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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...).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 28 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | Day 28 | 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. |
| 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). | Day 28 | 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. |
| 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). | Day 84 | 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. |
| Change in Speech Discrimination Threshold From Baseline to Day 28 | 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. |
| Change in Speech Discrimination Threshold From Baseline to Day 84 | 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. |
Countries
Bulgaria, Canada, Czechia, France, Germany, Israel, Serbia, Slovakia, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 29 mg Dose Group 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.
SENS-401: 29 mg dose group: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks | 38 |
| 43.5 mg Dose Group 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.
SENS-401: 43.5 mg dose groupe: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks | 39 |
| Placebo Oral Tablet Patients will receive the study drug (placebo) in the form of tablets by mouth, twice a day, during the first 4 weeks after randomization.
Placebo Oral Tablet: placebo, oral route, by mouth, twice a day, during 4 weeks | 38 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 | 0 |
| Overall Study | Other | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 5 | 3 |
Baseline characteristics
| Characteristic | 29 mg Dose Group | 43.5 mg Dose Group | Placebo Oral Tablet | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 3 Participants | 4 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 36 Participants | 34 Participants | 98 Participants |
| Age, Continuous | 56.0 years STANDARD_DEVIATION 16.4 | 46.9 years STANDARD_DEVIATION 16.01 | 49.8 years STANDARD_DEVIATION 14.56 | 50.3 years STANDARD_DEVIATION 15.86 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 36 Participants | 34 Participants | 36 Participants | 106 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | NA Participants | NA Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Ethnicity White | NA Participants | NA Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Race Hispanic or Latino | NA Participants | NA Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Race Not Hispanic or Latino | NA Participants | NA Participants | NA Participants | NA Participants |
| Race/Ethnicity, Customized Race Unknown | 5 Participants | 8 Participants | 2 Participants | 15 Participants |
| Race/Ethnicity, Customized Race White | 33 Participants | 31 Participants | 36 Participants | 100 Participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 9 Participants | 40 Participants |
| Sex: Female, Male Male | 24 Participants | 22 Participants | 29 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 20 / 38 | 13 / 39 | 4 / 38 |
| serious Total, serious adverse events | 1 / 38 | 1 / 39 | 1 / 38 |
Outcome results
Primary
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.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | 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). | -27.754 dB |
| 43.5 mg Dose Group | 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). | -24.931 dB |
| Placebo Oral Tablet | 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). | -25.214 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.3419Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.5181Mixed Models Analysis
Secondary
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.
Time frame: Day 28
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | 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). | -27.910 dB |
| 43.5 mg Dose Group | 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). | -24.468 dB |
| Placebo Oral Tablet | 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). | -25.726 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.3666Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.5776Mixed Models Analysis
Secondary
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.
Time frame: Day 84
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | 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). | -32.469 dB |
| 43.5 mg Dose Group | 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). | -30.070 dB |
| Placebo Oral Tablet | 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). | -25.399 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.1269Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.2257Mixed Models Analysis
Secondary
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.
Time frame: Day 28
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | 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). | -30.889 dB |
| 43.5 mg Dose Group | 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). | -30.035 dB |
| Placebo Oral Tablet | 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). | -29.371 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.4094Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.4602Mixed Models Analysis
Secondary
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.
Time frame: Day 28
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | Change in Speech Discrimination Threshold From Baseline to Day 28 | -22.899 dB |
| 43.5 mg Dose Group | Change in Speech Discrimination Threshold From Baseline to Day 28 | -19.882 dB |
| Placebo Oral Tablet | Change in Speech Discrimination Threshold From Baseline to Day 28 | -19.827 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.3121Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.4965Mixed Models Analysis
Secondary
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.
Time frame: Day 84
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 29 mg Dose Group | Change in Speech Discrimination Threshold From Baseline to Day 84 | -24.990 dB |
| 43.5 mg Dose Group | Change in Speech Discrimination Threshold From Baseline to Day 84 | -22.671 dB |
| Placebo Oral Tablet | Change in Speech Discrimination Threshold From Baseline to Day 84 | -16.642 dB |
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.0976Mixed Models Analysis
Comparison: The null and alternative hypotheses for Part 1 of the study were as follows, where μH, μL and μP were defined as the mean change in PTA of the high dose, low dose, and placebo respectively: H0H: μH - μP = 0, HAH: μH - μP \<0 (greater decrease on high dose) H0L: μL - μP = 0, HAL: μL - μP \<0 (greater decrease on low dose)p-value: 0.1762Mixed Models Analysis