Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss (AUDIBLE-S)

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

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

Study Overview

• Status: Completed
• Conditions: Severe Sudden Sensorineural Hearing Loss
• Intervention / Treatment: Drug: SENS-401; Drug: SENS-401; Other: Placebo Oral Tablet

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".

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Multiprofile Hospital for Active Treatment Burgas AD Department of Otorhynolaryngology
  • Sofia, Bulgaria, 1606
    • MI Minisrty of Interior Affair Sofia Clinic of Otorhinolaryngology
  • Sofia, Bulgaria, 1606
    • Military Medical Academy; Clinic of Otorhynolaryngology
• Canada
  • Québec, Canada, G1V 4G2
    • CHU de Quebec - Centre Hospitalier de l'Universite Laval
  • Saskatoon, Canada, S7K 1N4
    • Wall Street ENT Clinic
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice u sv. Anny v Brne-Klinika otorinolaryngologie a chirurgie hlavy a krku
  • Hradec Králové, Czechia
    • Fakultni nemocnice Hradec Kralove -Klinika otorinolaryngologie a chirurgie hlavy a krku
• France
  • Clamart, France, 92140
    • Hôpital d'Instruction des Armées PERCY
  • Marseille, France, 13003
    • Hôpital Européen
  • Paris, France, 75475
    • Hopital Lariboisiere
  • Saint-Maixent-l'École, France, 79400
    • 109ème Antenne Médicale de Saint-Maixent l'école
  • Sarrebourg, France, 57404
    • 43ème Antenne Médicale de Sarrebourg
  • Toulon, France, 83000
    • Hôpital d'Instruction des armées SAINTE ANNE
  • Toulouse, France, 31059
    • Hôpital Pierre Paul Riquet- CHU Purpan
• Germany
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen Klinik für Hals-, Nasen- u. Ohrenheilkunde Plastische Operationen
• Israel
  • Hadera, Israel, 38100
    • Hillel Yaffe Medical Center
  • Haifa, Israel, 3436212
    • Lady Davis Carmel Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center Health Care Campus
  • Petah tikva, Israel, 4341492
    • Rabin Medical Center, Otolaryngology, Head and Neck Surgery Gour Shasha Tower Building, floor#7
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Dr Dragisa Misovic-Dedinje
  • Novi Sad, Serbia, 21000
    • Clinical Center of Vojvodina
• Slovakia
  • Liptovský Mikuláš, Slovakia, 03101
    • MUDr. Igor Kažmér, s.r.o.
  • Prešov, Slovakia, 08001
    • Fakultna nemocnica s poliklinikou J. A. Reimana Presov, Oddelenie otorinolaryngologie a chirurgie hlavy a krku
• Turkey
  • Istanbul, Turkey, 34722
    • Istanbul Medeniyet University Goztepe Training and Research Hospital, Department of Ear,Nose,Throat
  • Melikgazi, Turkey, 38039
    • Erciyes University Medical Faculty Department of Ear Nose Throat
• United Kingdom
  • Sheffield, United Kingdom, S10 2JF
    • The Royal Hallamshire Hospital

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

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...).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: SENS-401; 29 mg dose group: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks; Drug: SENS-401; 43.5 mg dose groupe: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks
Experimental: 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.	Drug: SENS-401; 29 mg dose group: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks; Drug: SENS-401; 43.5 mg dose groupe: tablets of 14.5 mg, oral route, by mouth, twice a day, during 4 weeks
Placebo Comparator: 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.	Other: Placebo Oral Tablet; placebo, oral route, by mouth, twice a day, during 4 weeks

What is the study measuring?

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 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
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

Collaborators and Investigators

• Sponsor: Sensorion
• Investigators: Study Director: Géraldine HONNET, MD, Sensorion

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Actual): November 4, 2021
• Study Completion (Actual): January 12, 2022

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• 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: SENS 401-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No