SPI-1005 for the Treatment of Meniere's Disease (STOPMD-3)

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

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.

Study Overview

• Status: Completed
• Conditions: Meniere Disease; Ménière
• Intervention / Treatment: Drug: Ebselen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90057
      • House Clinic
    • Roseville, California, United States, 95661
      • Sacramento Ear, Nose, & Throat
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
  • Florida
    • Boca Raton, Florida, United States, 33487
      • ENT and Allergy Associates of Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Advanced ENT & Allergy
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Ear, Nose & Throat Associates
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19144
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Sound Pharmaceuticals, Incorporated

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Actual): September 19, 2023
• Study Completion (Actual): July 25, 2024

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: vertigo; tinnitus; hearing loss; dizziness; ebselen; SPI-1005
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Endolymphatic Hydrops; Meniere Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents; Anti-Ulcer Agents; Antioxidants; Ebselen
• Other Study ID Numbers: SPI-1005-351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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