Meniere's DiseasePhase 3AVERTS-2NCT02717442

Study of OTO-104 in Subjects With Unilateral Meniere's Disease

A Phase 3 study testing OTO-104 in people with Meniere's Disease, run by Otonomy, Inc. at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

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

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Meniere's Disease
What is being tested?: OTO-104
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 176 participants
Where: 1 siteUnited States
Study dates: 21 Mar 2016to 15 Sep 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

Other trials in United States

About this study

Official title: 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.

Conditions: Meniere's Disease
Being tested: OTO-104, Placebo
Keywords: Meniere's Disease, Vertigo
Medical subject headings: Meniere Disease, Vertigo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OTO-104Drug
Single intratympanic injection of 12 mg OTO-104
PlaceboDrug
Single intratympanic injection of placebo

Study groups in NCT02717442
Study group	Role	What they receive
OTO-104	Experimental	12 mg dexamethasone Receives: Drug: OTO-104
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 3 months

Secondary outcomes (6)

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
1. = slight limitation
2. = moderate limitation
3. = sick at home
4. = bedridden
Measured: 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
1. = slight limitation
2. = moderate limitation
3. = sick at home
4. = bedridden
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Mar 201615 Sep 2017

First posted23 Mar 2016 (estimated)
Study start21 Mar 2016
Primary completion31 Aug 2017
Study completion15 Sep 2017

Why it stopped: Negative Efficacy Results from the recently completed Phase 3 study 104-201506

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Meniere's DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 176 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02717442
Sponsor's protocol ID: 104-201508
Acronym: AVERTS-2
Status last verified: Dec 2022
First submitted: 10 Mar 2016
Last updated: 13 Jan 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Phillips J, Mikulec AA, Robinson JM, Skarinsky D, Anderson JJ. Efficacy of Intratympanic OTO-104 for the Treatment of Meniere's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies. Otol Neurotol. 2023 Jul 1;44(6):584-592. doi: 10.1097/MAO.0000000000003886. Epub 2023 Apr 22.
PubMed 37185596

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
CI Following VS Removal or Labyrinthectomy
Vestibular Schwannoma, Meniere Disease
Active, not recruitingPhase 3
SPI-1005 for the Treatment of Meniere's Disease (Open Label)
Meniere's Disease, Ménière's Disease
RecruitingObservational study
Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures, and Discovery of Therapeutic Targets
Meniere's Disease, Enlarged Vestibular Aqueduct Syndrome
RecruitingPhase 4
Treatment of Meniere's Disease With Migraine Medications
Ménière
RecruitingPhase 2
Effects of Anakinra in Subjects With Corticosteroid-resistant/Intolerant Meniere's Disease and Autoimmune Inner Ear Disease
Autoimmune Inner Ear Disease, Meniere's Disease

All Meniere's Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02717442
Acronym / sponsor ID: AVERTS-2 / 104-201508
Conditions: Meniere's Disease
Keywords: Meniere's Disease, Vertigo
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Negative Efficacy Results from the recently completed Phase 3 study 104-201506
Enrolment: 176 participants (actual)
Lead sponsor: Otonomy, Inc.Industry (pharma, biotech, devices)
Study start: 21 Mar 2016 (actual)
Primary completion: 31 Aug 2017 (actual)
Study completion: 15 Sep 2017 (actual)
First posted: 23 Mar 2016 (estimated)
Results: Posted 13 Jan 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
OTO-104	Experimental	Drug: OTO-10412 mg dexamethasone
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OTO-104Single intratympanic injection of 12 mg OTO-104	Drug	OTO-104
PlaceboSingle intratympanic injection of placebo	Drug	Placebo

Primary outcome

The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-1 Population
Time frame: 3 months
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.
The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-2 Population
Time frame: 3 months
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.

6 secondary outcomes

Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-1
Time frame: 3 months
Effect of Vertigo on Daily Activities - Number of Days Sick at Home or Bedridden at Week 12 (Month 3): FAS-2
Time frame: 3 months
Otoscopic Examination - Tympanic Membrane Perforation at Week 12 (Month 3)
Time frame: 3 months
Audiometry - Shift in Air-Bone Gap at 500 Hz From Baseline to Week 12 (Month 3)
Time frame: 3 Months
Audiometry - Shift in Air-Bone Gap at 1000 Hz From Baseline to Week 12 (Month 3)
Time frame: 3 months
Audiometry - Shift in Air-Bone Gap at 2000 Hz From Baseline to Week 12 (Month 3)
Time frame: 3 months

Results and safety

Results posted to the registry on 13 Jan 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OTO-104	88	53
Placebo	88	59

Primary outcome: The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-1 Population

Time frame: 3 months. Mean (95% Confidence Interval). Unit: Definitive Vertigo Day

Measure	OTO-104 (Full Analysis Set -1) n = 86	Placebo (Full Analysis Set - 1) n = 88
Value	2.336 (1.747 to 3.125)	3.549 (2.763 to 4.560)

OTO-104 (Full Analysis Set -1) vs Placebo (Full Analysis Set - 1): Risk Ratio (RR): 0.658 (95% CI 0.453 to 0.957), p =0.029, Regression, Linear

Population analysed: A subject is included in the analysis if they received study drug, had a baseline definitive vertigo measurement for the 4-week lead-in period and at least one 4-week definitive vertigo measurement post-baseline, i.e., at least one post-baseline daily diary entry. The model and corresponding method of estimation adjusted for overdispersion and addressed missing 4-week intervals under the assumption of Missing at Random (MAR).

Primary outcome: The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-2 Population

Time frame: 3 months. Mean (95% Confidence Interval). Unit: Definitive Vertigo Day

Measure	OTO-104 (Full Analysis Set -2) n = 55	Placebo (Full Analysis Set - 2) n = 56
Value	2.044 (1.480 to 2.822)	3.467 (2.617 to 4.594)

OTO-104 (Full Analysis Set -2) vs Placebo (Full Analysis Set - 2): Risk Ratio (RR): 0.590 (95% CI 0.388 to 0.896), p =0.014, Regression, Linear

Population analysed: The FAS - 2 includes all subjects from FAS-1 who were randomized 12 weeks prior to the study termination decision date of August 31, 2017 (i.e., subjects that had the opportunity to complete 12 weeks of daily diary entries in the study at the time of study termination).

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Reported or observed during or after dosing with the study drug at the Baseline visit up until the Week 12 (3 Months) end of study visit. The Baseline visit occurred at the end of lead-in. No intervention was administered during lead-in, which is why adverse events were collected starting at the Baseline visit during dosing up until the final visit.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OTO-104 (Safety Analysis Set)	2 of 86 (2.3%)	52 of 86 (60.5%)	0 of 86
Placebo (Safety Analysis Set)	0 of 88 (0%)	29 of 88 (33%)	0 of 88

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37185596Phillips J, Mikulec AA, Robinson JM, Skarinsky D, Anderson JJ. Efficacy of Intratympanic OTO-104 for the Treatment of Meniere's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies. Otol Neurotol. 2023 Jul 1;44(6):584-592. doi: 10.1097/MAO.0000000000003886. Epub 2023 Apr 22.

Related trials for Meniere's Disease

Active, not recruiting
CI Following VS Removal or Labyrinthectomy
Vestibular Schwannoma, Meniere Disease
Active, not recruitingPhase 3
SPI-1005 for the Treatment of Meniere's Disease (Open Label)
Meniere's Disease, Ménière's Disease
RecruitingObservational study
Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures, and Discovery of Therapeutic Targets
Meniere's Disease, Enlarged Vestibular Aqueduct Syndrome
RecruitingPhase 4
Treatment of Meniere's Disease With Migraine Medications
Ménière
RecruitingPhase 2
Effects of Anakinra in Subjects With Corticosteroid-resistant/Intolerant Meniere's Disease and Autoimmune Inner Ear Disease
Autoimmune Inner Ear Disease, Meniere's Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kathie Bishop, PhD study chair

Otonomy, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing OTO-104 in people with Meniere's Disease, run by Otonomy, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Number of DVD at Week 12 (the 4-week [28 Days] Interval From Week 9 Through Week 12) - FAS-1 Population (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02717442, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2023.