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

A Phase I & II Open-label Study of the Effects of Anakinra (Kineret) in Corticosteroid-resistant Subjects With Sudden Sensorineural Heaing Loss (SSNHL)

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.

Study Overview

• Status: Terminated
• Conditions: Hearing Loss, Sudden
• Intervention / Treatment: Drug: anakinra

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore-LIJ Hearing and Speech Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anakinra; 100mg of Anakinra administered as a daily subcutaneous injection	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; Other Names: Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to Anakinra in Corticosteroid Resistant Patients With SSNHL	Patients who had a response to anakinra based on hearing threshold improvement compared to their pre-treatment threshold.	120 days

Collaborators and Investigators

• Sponsor: Andrea Vambutas
• Investigators: Principal Investigator: Andrea Vambutas, MD, Northwell Health

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: February 23, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sudden; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 13-333B