Study of OTO-104 in Subjects With Unilateral Meniere's Disease (AVERTS-2)

A Prospective, Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of OTO-104 Given as a Single Intratympanic Injection in Subjects With Unilateral Meniere's Disease

The purpose of this study is to evaluate the effectiveness of OTO-104 for the treatment of Meniere's disease.

Study Overview

• Status: Terminated
• Conditions: Meniere's Disease
• Intervention / Treatment: Drug: Placebo; Drug: OTO-104

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92121
      • Many sites in Europe. Refer to the contact info listed below.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria includes, but is not limited to:

• Subject has a diagnosis of unilateral Meniere's disease by 1995 American Academy of Otolaryngology - Head and Neck Surgery (AAOHNS) criteria and reports active vertigo for the 2 months prior to the study lead-in period.
• Subject has experienced active vertigo during the lead-in period.
• Subject has documented asymmetric sensorineural hearing loss.
• Subject agrees to maintain their current treatments for Meniere's disease while on-study.

Exclusion Criteria includes, but is not limited to:

• Subject is pregnant or lactating.
• Subject has a history of immunodeficiency disease.
• Subject has a history of previous endolymphatic sac surgery.
• Subject has a history of previous use of intratympanic (IT) gentamicin in the affected ear.
• Subject has a history of tympanostomy tubes with evidence of perforation or lack of closure.
• Subject has experienced an adverse reaction to IT injection of steroids.
• Subject has used an investigational drug or device in the 3 months prior to screening.
• Subject has previously been randomized to a trial of OTO-104.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Single intratympanic injection of placebo
Experimental: OTO-104; 12 mg dexamethasone	Drug: OTO-104; Single intratympanic injection of 12 mg OTO-104

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-1 Population	In the Full Analysis Set (FAS)-1 population, the number of DVDs at Week 12 (the 4-week [28 days] interval from Week 9 through Week 12) was compared between OTO-104 and placebo. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 months
The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-2 Population	The number of DVDs at Week 12 (the 4-week [28 days] interval from Week 9 through Week 12) was compared between OTO-104 and placebo. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-1	Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in. Questionnaire - subjects were instructed to record the effect on their daily activities of their total vertigo experienced that day using a 5-point scoring system: 0 = normal activity; = slight limitation; = moderate limitation; = sick at home; = bedridden	3 months
Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-2	Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in. Questionnaire - subjects were instructed to record the effect on their daily activities of their total vertigo experienced that day using a 5-point scoring system: 0 = normal activity; = slight limitation; = moderate limitation; = sick at home; = bedridden	3 months
Otoscopic Examination - Tympanic Membrane Perforation at Week 12 (Month 3)	Otoscopic examinations were conducted at each visit. It was considered important to understand if the tympanic perforation that resulted from the IT injection at the Baseline visit persisted at the end of study visit (Week12 [Month 3]). Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 months
Audiometry - Shift in Air-Bone Gap at 500 Hz From Baseline to Week 12 (Month 3)	The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment (<=10 dB) to impairment (>10 dB) when measure at 500 Hz. Week 12 = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 Months
Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3)	The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (<= 10 dB) to impairment at Month 3 (>10 dB) when measured at 1000 Hz. Week 12 (Month 3) = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 months
Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3)	The number of subjects with a change in air-bone gap from Baseline to Week 12 (Month 3) from no impairment at baseline (<= 10 dB) to impairment at Month 3 (>10 dB) when measured at 2000 Hz. Week 12 (Month 3) = 12 weeks after dosing at the Baseline visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in.	3 months

Collaborators and Investigators

• Sponsor: Otonomy, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2016
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): September 15, 2017

Study Registration Dates

• First Submitted: March 10, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimate): March 23, 2016

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Vertigo; Meniere's Disease
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Labyrinth Diseases; Ear Diseases; Endolymphatic Hydrops; Meniere Disease
• Other Study ID Numbers: 104-201508