SPI-1005 for the Treatment of Meniere's Disease

Study Overview
=================
Brief Summary
-----------------
The study is a randomized, double-blind, placebo-controlled, multi-center clinical trial (RCT) with open-label extension study (OLE), of SPI-1005 in adult subjects with definite Meniere's disease with active symptoms within three months preceding study enrollment.

Official Title
-----------------
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of SPI-1005 in Meniere's Disease and Open Label Extension Study to Evaluate the Chronic Safety of SPI-1005

Conditions
-----------------
Meniere Disease, Ménière

Intervention / Treatment
-----------------
* Drug: Ebselen
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPI-1005 400 mg BID<br>Oral administration of SPI-1005 400 mg BID for 28 days, with 84-day followup | Drug: Ebselen<br>* Glutathione peroxidase mimetic<br>* Other names: SPI-1005;|
| Placebo Comparator: Placebo<br>Oral administration of matching placebo BID for 28 days, with 84-day followup | Drug: Placebo<br>* Matching placebo containing excipients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Safety and tolerability assessed based on comparison of adverse events vs. placebo | 84 days | 
| Change in low frequency hearing thresholds measured by pure tone audiometry | Co-primary efficacy endpoint; assessment of hearing by pure tone audiometry | 56 days | 
| Change in Words-in-Noise Test score | Co-primary efficacy endpoint; assessment of word recognition by Words-in-Noise Test | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tinnitus severity | Tinnitus Functional Index (0-100) where higher score is worse outcome | 56 days | 
| Change in tinnitus loudness | Tinnitus Functional Index Question #2 -- How Strong or Loud was your Tinnitus? (0-10) where higher score is worse outcome | 56 days | 
| Change in vertigo severity | Vertigo Symptom Scale (0-60) where higher score is worse outcome | 56 days | 
| Change in aural fullness | Aural Fullness Scale (0-10) where higher score is worse outcome | 56 days | 
| Change in dizziness | Dizziness Handicap Inventory (0-100) where higher score is worse outcome | 56 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ebselen, hearing loss, tinnitus, vertigo, dizziness, SPI-1005