Clinical trial NCT02414152: Study of the Effects of Anakinra in Corticosteroid-resistant Subjects With Sudden Sensorineural Hearing Loss
Official title: A Phase I & II Open-label Study of the Effects of Anakinra (Kineret) in Corticosteroid-resistant Subjects With Sudden Sensorineural Heaing Loss (SSNHL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hearing Loss, Sudden
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2015-04-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if anakinra (an interleukin-1 receptor antagonist) can improve hearing thresholds in patients with sudden sensorineural hearing loss that did not respond to oral steroid therapy. 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.

The investigators will be measuring hearing thresholds (Pure tone average and word recognition scores) before and after anakinra and correlating these findings with circulating IL-1 levels in the patient's blood.

Detailed description: For patients that experience an acute, sensorineural decline in hearing, timely corticosteroid administration may result in preservation of some or all of the hearing. For patients with sudden sensorineural hearing loss who have failed to respond to corticosteroid therapy, this study will be offered to determine if anakinra is a safe and effective alternative therapy for clinical hearing restoration. The investigators have previously demonstrated that IL-1beta inhibition (with anakinra) in a small cohort of patients with steroid resistant autoimmune inner ear disease was effective in demonstrating audiological improvements.

Eligibility criteria: Inclusion Criteria:

1. Patients must have Sudden Sensorineural Hearing Loss in one ear, with a no greater than 25 dB PTA in the contralateral ear.
2. Age and Gender: male and female subjects, age ≥ 18 but ≤ 75, will be recruited.
3. Patients must be capable of understanding and giving informed consent.
4. Patients must have SNHL of greater than or equal to 30dB at three contiguous frequencies in one ear which evolved in three days or less, with a PTA of 25dB or less in the contralateral ear.
5. Patients must have previously undergone a trial of high-dose corticosteroid therapy, at 60 mg daily for a minimum of seven days, with a variable taper thereafter that consists of a total of 14 consecutive days of corticosteroid use. Patients must have demonstrated less than a 5 decibel average improvement in their PTA in response to corticosteroids as measured by their audiogram.
6. NO greater than 30 days may elapse from the discontinuation from the initial course of steroid treatment to the time of enrollment.

Exclusion Criteria:

1. Patients over 75 years of age, because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly.
2. Patients with evidence of retrocochlear pathology (vestibular schwannoma) or inner ear malformation (Mondini Malformation or Enlarged Vestibular Aqueduct) based on imaging.
3. Patients concurrently receiving methotrexate or TNF-antagonist therapy.
4. Patients with a diagnosis of any immunodeficiency syndrome.
5. Patients with active or chronic infections.
6. Patients currently receiving, or having received treatment for a malignancy in the past three years.
7. Patients with a diagnosis of chronic renal insufficiency (a creatinine clearance of \<49mL/min) or chronic renal failure.
8. Patients with evidence of neutropenia (an ANC of \<1000) prior to treatment with anakinra.
9. Known hypersensitivity to E. coli derived products.
10. Latex sensitivity.
11. Any patient that received a live vaccine \< 3 months prior to enrollment.
12. Any patient with a history of active narcotic abuse, including prescription narcotics.
13. Pregnant or lactating females.
14. Children, \< age 18
15. .Non-English speaking patients, as the word recognition scoring is in English and is a vital component to the efficacy analysis.
16. Any patient that tests positive for Hepatitis B, C, HIV or tuberculosis on screening, with the exception of presence of antibodies to Hepatitis B in subjects reporting prior vaccination, and presence of positive skin testing for TB in subjects who received BCG in the past.

Primary outcomes:
measure: Response to Anakinra in Corticosteroid Resistant Patients With SSNHL
timeFrame: 120 days
Secondary outcomes:
Other outcomes:
Locations:
city: New Hyde Park
country: United States
facility: North Shore-LIJ Hearing and Speech Center
state: New York
Study officials:
affiliation: Northwell Health
name: Andrea Vambutas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.