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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Open-label Study of the Effects of Anakinra in Corticosteroid-resistant Subjects With Autoimmune Inner Ear Disease

Conditions
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Sensorineural Hearing Loss, Autoimmune Inner Ear Disease

Intervention / Treatment
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* Drug: Anakinra


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm-Open Label<br>Single Arm-Open Label use of Anakinra | Drug: Anakinra<br>* 100mg of anakinra administered by a subcutaneous injection for 84 consecutive days.<br>* Other names: Kineret;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Potential Efficacy of Anakinra in Improving Hearing Thresholds in Corticosteroid-resistant Patients With Autoimmune Inner Ear Disease | 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. | 180 days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steroid, Steroid-Resistant, Autoimmune Inner Ear Disease, Immune Mediated Hearing Loss, Sudden Sensorineural Hearing Loss, Meniere's Disease, Autoimmune, Hearing