Autoimmune Inner Ear Disease, Sensorineural Hearing Loss
Conditions
Keywords
Steroid, Steroid-Resistant, Autoimmune Inner Ear Disease, Immune Mediated Hearing Loss, Sudden Sensorineural Hearing Loss, Meniere's Disease, Autoimmune, Hearing
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.
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.
Interventions
DRUGAnakinra
100mg of anakinra administered by a subcutaneous injection for 84 consecutive days.
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
Andrea Vambutas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Patients with Autoimmune Inner Ear Disease that had \<5dB hearing improvement in response to corticosteorids following 28 days of treatment | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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.
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | To Assess the Potential Efficacy of Anakinra in Improving Hearing Thresholds in Corticosteroid-resistant Patients With Autoimmune Inner Ear Disease | 7 responders |
Secondary
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
Time frame: 84 days
Population: Any subject enrolled in this study who received at least 1 injection dose of anakinra
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm | Number of Serious Adverse Events Reported | 0 reported SAEs |