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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	13 participants
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 :	June 2011
Actual Primary Completion Date :	September 2014
Actual Study Completion Date :	September 2014

Arms and Interventions

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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 Name: Kineret

Outcome Measures

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Primary Outcome Measures :

1. To Assess the Potential Efficacy of Anakinra in Improving Hearing Thresholds in Corticosteroid-resistant Patients With Autoimmune Inner Ear Disease [ Time Frame: 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 [ Time Frame: 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

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Ages Eligible for Study:	13 Years to 75 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, New York
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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Clinical trials at the Feinstein Institute for Medical Research 

Publications of Results:

Vambutas A, Lesser M, Mullooly V, Pathak S, Zahtz G, Rosen L, Goldofsky E. Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. J Clin Invest. 2014 Sep;124(9):4115-22. doi: 10.1172/JCI76503. Epub 2014 Aug 18.

Responsible Party:	Andrea Vambutas, Professor of Otolaryngology & Molecular Medicine, Northwell Health
ClinicalTrials.gov Identifier:	NCT01267994 History of Changes
Other Study ID Numbers:	1R21DC011827-01 ( U.S. NIH Grant/Contract ); R33DC011827 ( U.S. NIH Grant/Contract )
First Posted:	December 29, 2010
Results First Posted:	April 6, 2015
Last Update Posted:	January 10, 2018
Last Verified:	December 2017

Keywords provided by Andrea Vambutas, 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; Hearing Disorders; Otorhinolaryngologic Diseases	Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Otitis; Interleukin 1 Receptor Antagonist Protein; Antirheumatic Agents