A Clinical Trial of Anakinra for Steroid-Resistant Autoimmune Inner Ear Disease

• Sponsor: Andrea Vambutas (Other)
• Overall Status: Completed
• CT.gov ID: NCT01267994
• Collaborator: National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if Anakinra (an interleukin-1 receptor antagonist) can improve hearing thresholds in those patients with Autoimmune Inner Ear Disease (AIED) that did not respond to oral steroid therapy for a sudden decline in hearing. The patients to be enrolled will have recently completed a course of oral steroids and demonstrated no change in their audiometric thresholds following corticosteroid therapy.

Condition or Disease	Intervention/Treatment	Phase
Sensorineural Hearing Loss; Autoimmune Inner Ear Disease	Drug: Anakinra	Phase 1/Phase 2

Detailed Description

Patients with immune mediated hearing loss (also known as autoimmune hearing loss) are typically treated with corticosteroids. Of those treated, approximately 60% respond, however, that response may be lost over time. Other therapies use to date have proven largely ineffectual in improving hearing. This study proposes a phase I open label clinical trial of Anakinra for corticosteroid-resistant patients to determine if this therapy is efficacious in hearing restoration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Open-label Study of the Effects of Anakinra in Corticosteroid-resistant Subjects With Autoimmune Inner Ear Disease
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm-Open Label Single Arm-Open Label use of Anakinra	Drug: Anakinra; 100mg of anakinra administered by a subcutaneous injection for 84 consecutive days.; Other Names: Kineret

Outcome Measures

Primary Outcome Measures

1. To Assess the Potential Efficacy of Anakinra in Improving Hearing Thresholds in Corticosteroid-resistant Patients With Autoimmune Inner Ear Disease [180 days]

   The primary endpoint is to determine whether those treated with anakinra for 84 days demonstrate an improved hearing threshold compared with their pre-anakinra-treatment threshold. Audiometric thresholds will be compared to those treated with a prolonged corticosteroid taper and those that elect for no further treatment. The durability of the response will be measured over a total of 180 days.

Secondary Outcome Measures

1. Number of Serious Adverse Events Reported [84 days]

   To assess the number of Serious Adverse Events reported in any subject that received at least one injection dose of anakinra

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Bilateral sensorineural hearing loss with an active decline in hearing in one ear

• No audiometric improvement with 28-30 days of oral prednisone or other corticosteroid, including an initial dose of 60mg per day for 14 days

• Enrollment within 14 days of completion of corticosteroid therapy

• Age 13 years and older

• No evidence of neutropenia (low white blood cell count)

• No evidence of retrocochlear pathology (ie. acoustic neuroma/vestibular schwannoma)

• May have concurrent, systemic autoimmune disease

Exclusion Criteria:

• Age over 75, or less than 13

• Neutropenia

• Renal insufficiency

• Pregnant females

• Unilateral hearing loss

• Patients with any immunodeficiency syndrome

• Patients receiving methotrexate or any TNF (tumor necrosis factor) antagonist therapy

• Patients with chronic infections

• Patients treated for a malignancy within the past 3 years

• Patients with a latex allergy

• Patients with an inner ear anomaly

• Patients with retrocochlear pathology

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Shore-LIJ Hearing and Speech Center	New Hyde Park	New York	United States	11040

Sponsors and Collaborators

• Andrea Vambutas
• National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

• Principal Investigator: Andrea Vambutas, MD, Northwell Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trials at the Feinstein Institute for Medical Research

Publications

None provided.

• Responsible Party: Andrea Vambutas, Professor of Otolaryngology & Molecular Medicine, Northwell Health
• ClinicalTrials.gov Identifier: NCT01267994
• Other Study ID Numbers: 1R21DC011827-01; R33DC011827
• First Posted: Dec 29, 2010
• Last Update Posted: Jan 10, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Andrea Vambutas, Professor of Otolaryngology & Molecular Medicine, Northwell Health: Steroid; Steroid-Resistant; Autoimmune Inner Ear Disease; Immune Mediated Hearing Loss; Sudden Sensorineural Hearing Loss; Meniere's Disease; Autoimmune; Hearing
• Additional relevant MeSH terms: Hearing Loss; Deafness; Hearing Loss, Sensorineural; Ear Diseases; Labyrinth Diseases; Labyrinthitis; Interleukin 1 Receptor Antagonist Protein

Study Results

Participant Flow

Arm/Group Title	Open Label Trial
Arm/Group Description	Open label, single arm trial of anakinra for corticosteroid-resistant Autoimmune Inner Ear Disease
Period Title: Overall Study
STARTED	12
COMPLETED	10
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	Patients with Autoimmune Inner Ear Disease that had <5dB hearing improvement in response to corticosteorids following 28 days of treatment
Overall Participants	13
Age (Count of Participants)
<=18 years	1 7.7%
Between 18 and 65 years	12 92.3%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	6 46.2%
Male	7 53.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	13 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	13 100%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	To Assess the Potential Efficacy of Anakinra in Improving Hearing Thresholds in Corticosteroid-resistant Patients With Autoimmune Inner Ear Disease
Description	The primary endpoint is to determine whether those treated with anakinra for 84 days demonstrate an improved hearing threshold compared with their pre-anakinra-treatment threshold. Audiometric thresholds will be compared to those treated with a prolonged corticosteroid taper and those that elect for no further treatment. The durability of the response will be measured over a total of 180 days.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm
Arm/Group Description	Patients with Autoimmune Inner Ear Disease that had <5dB hearing improvement in response to corticosteorids following 28 days of treatment
Measure Participants	10
Number [responders]	7

2. Secondary Outcome

Title	Number of Serious Adverse Events Reported
Description	To assess the number of Serious Adverse Events reported in any subject that received at least one injection dose of anakinra
Time Frame	84 days

Outcome Measure Data

Analysis Population Description

Any subject enrolled in this study who received at least 1 injection dose of anakinra

Arm/Group Title	Single Arm
Arm/Group Description	Subject who received at least one injection of anakinra
Measure Participants	12
Number [reported SAEs]	0

Adverse Events

Arm/Group Title	Single Arm
Arm/Group Description	Anakinra administered for 84 consecutive days
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)
Ear and labyrinth disorders
Tinnitus	2/12 (16.7%)
Eye disorders
Visual Impairment	1/12 (8.3%)
Gastrointestinal disorders
Nausea	2/12 (16.7%)
Nervous system disorders
Headache	4/12 (33.3%)
Vertigo	3/12 (25%)
Respiratory, thoracic and mediastinal disorders
Influenza like illness	1/12 (8.3%)
Sinusitis	1/12 (8.3%)
Wheezing	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Injection site reactions	10/12 (83.3%)
Cellulitis	1/12 (8.3%)
Psoriasis Flare	1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.