Study of the Effects of Anakinra in Corticosteroid-resistant Subjects With Sudden Sensorineural Hearing Loss

Hearing Loss, Sudden Clinical Trial

— SSNHL  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02414152
• Other study ID #: 13-333B
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 23, 2015
• Last updated: September 8, 2015
• Start date: October 2013
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Hearing Loss, Sudden

Intervention

Drug:
• anakinra
100mg of anakinra adminstered by a subcutaneous injection for a minimum of 28 days, retreatment with additional 28 day cycle based on clinical response

Locations

Country	Name	City	State
United States	North Shore-LIJ Hearing and Speech Center	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Andrea Vambutas

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measurement of circulating or induced IL-1beta expression is predictive of clinical hearing recovery	Research bloods to measure circulating IL-1beta levels will be drawn at each visit	120 days	No
Primary	Primary measure will be the "response" at Day 28, 56 and 84 which will be defined as an improvement in PTA (>5db at the average of 250,500,1000,2000 and 4000Hz) or WRS (greater or equal to 12%)	Patients will be treated with 28 consecutive injections of anakinra, a hearing reassessment at days 28, 56 and 84. If a positive complete response, as measured by the protocol, is seen at day 28, no further therapy will be instituted and the patient will be reassessed at day 56. If an incomplete or no response is seen at day 28, an additional 28 day cycle of anakinra will be administered.	120 days	No
Secondary	Retreatment of relapsed subjects who had previously were determined to be complete responders	Patients who had a complete positive response at day 28, maintained at day 56, but lost by day 84 will be retreated with an additional 28 day course of anakinra	120 days	Yes