SPI-1005 for the Treatment of Meniere's Disease

• Ebselen (Drug), also known as SPI-1005: Glutathione peroxidase mimetic
• Placebo (Drug): Matching placebo containing excipients

Primary outcomes

• Number of Participants With Treatment-Emergent Adverse Events [84 days]: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
• Change in Low Frequency Hearing Thresholds Measured by Pure Tone Audiometry [84 days]: Co-primary efficacy endpoint; assessment of hearing by pure tone audiometry
• Change in Words-in-Noise Test Score [84 days]: Co-primary efficacy endpoint; assessment of speech discrimination by Words-in-Noise (WIN) Test (WIN Score Improvement from Baseline >=4 words) The Words-in-Noise (WIN) test is a speech discrimination test which involves the presentation of specific words against a background noise (multi-talker babble). A total of 35 words are presented to each ear, with 5 words presented at each of 7 different signal-to-noise ratios representing increasing difficulty as the test progresses. The WIN Score is the sum total number of words correct (minimum 0, maximum 35) for each ear. A higher WIN Score is considered to be a better outcome. A WIN Score Improvement is an increase in score from baseline. The co-primary efficacy endpoint is the number of participants who had a WIN Score Improvement from Baseline of >=4 words out of the maximum of 35 words, in one or both ears.

Secondary outcomes

• Change in Tinnitus Severity [84 days]: Tinnitus Functional Index (0-100) where higher score is worse outcome. Mean change from baseline is reported, where a decrease in score is a better outcome.
• Change in Tinnitus Loudness [84 days]: Tinnitus Functional Index Question #2 -- How Strong or Loud was your Tinnitus? (0-10) where higher score is worse outcome. Mean change from baseline is reported, where a decrease in score is a better outcome.
• Change in Vertigo Severity [84 days]: Vertigo Symptom Scale (0-60) where higher score is worse outcome. Mean change from baseline is reported, where a decrease in score is a better outcome.
• Change in Aural Fullness [84 days]: Aural Fullness Scale (0-10) where higher score is worse outcome. Mean change from baseline is reported, where a decrease in score is a better outcome.
• Change in Dizziness [84 days]: Dizziness Handicap Inventory (0-100) where higher score is worse outcome. Mean change from baseline is reported, where a decrease in score is a better outcome.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Adult males/females, 18-75 years of age at the time of enrollment.
* Diagnosis of definite Meniere's Disease by AAO-HNS Amended 2015 Criteria.
* Hearing loss of ≥30 dB at 250, 500, or 1000 Hz at study enrollment.
* At least two of three active symptoms (tinnitus; aural fullness; vertigo or dizziness) of Meniere's disease by AAO-HNS Amended 2015 Criteria, within 3 months of study enrollment.

Exclusion Criteria:

* Current, or within 60 days prior to study enrollment, use of IV ototoxic medications
* History of otosclerosis or vestibular schwannoma.
* History of significant middle ear or inner ear surgery in the affected ear.
* Conductive hearing loss with air-bone gap ≥15 dB, otitis media, or mixed hearing loss.
* Significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, neurological, or psychiatric disease.
* Current use or within 30 days prior to study enrollment systemic steroids.
* Current use or within 7 days prior to study enrollment intratympanic steroids.

Participant flow

Outcome results

• Number of Participants With Treatment-Emergent Adverse Events (Primary), Count of participants, Participants: SPI-1005 400 mg BID 59; Placebo 45
• Change in Low Frequency Hearing Thresholds Measured by Pure Tone Audiometry (Primary), Count of participants, Participants: SPI-1005 400 mg BID 59; Placebo 40
• Change in Words-in-Noise Test Score (Primary), Count of participants, Participants: SPI-1005 400 mg BID 45; Placebo 30
• Change in Tinnitus Severity (Secondary), Mean, scores on a scale: SPI-1005 400 mg BID -7.9 +/- 20.42; Placebo -6.6 +/- 16.15
• Change in Tinnitus Loudness (Secondary), Mean, scores on a scale: SPI-1005 400 mg BID -0.8 +/- 2.22; Placebo -0.9 +/- 2.16
• Change in Vertigo Severity (Secondary), Mean, scores on a scale: SPI-1005 400 mg BID -0.3 +/- 1.16; Placebo -0.1 +/- 1.43
• Change in Aural Fullness (Secondary), Mean, scores on a scale: SPI-1005 400 mg BID -1.2 +/- 3.00; Placebo -0.6 +/- 2.65
• Change in Dizziness (Secondary), Mean, scores on a scale: SPI-1005 400 mg BID -5.9 +/- 14.71; Placebo -6.1 +/- 14.88

Adverse events

Time frame: SPI-1005 400 mg BID & Placebo: 3 months Open Label Extension: SPI-1005 400 mg BID: 6 to 12 months

Serious adverse events by term

Other adverse events by term

• Kil J, Harruff EE, Longenecker RJ. Development of ebselen for the treatment of sensorineural hearing loss and tinnitus. Hear Res. 2022 Jan;413:108209. doi: 10.1016/j.heares.2021.108209. Epub 2021 Feb 19. PMID 33678494
• Kil J, Pierce C, Tran H, Gu R, Lynch ED. Ebselen treatment reduces noise induced hearing loss via the mimicry and induction of glutathione peroxidase. Hear Res. 2007 Apr;226(1-2):44-51. doi: 10.1016/j.heares.2006.08.006. Epub 2006 Oct 6. PMID 17030476
• Kil J, Lobarinas E, Spankovich C, Griffiths SK, Antonelli PJ, Lynch ED, Le Prell CG. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2017 Sep 2;390(10098):969-979. doi: 10.1016/S0140-6736(17)31791-9. Epub 2017 Jul 14. PMID 28716314

• Study Protocol (PDF, 2021-04-08)
• Statistical Analysis Plan (PDF, 2024-09-20)