Effects of Anakinra in Subjects With Corticosteroid-resistant/Intolerant Meniere's Disease and Autoimmune Inner Ear Disease

NCT03587701 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-0195
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase II randomized, placebo controlled study design of anakinra (Kineret) in corticosteroid-resistant or intolerant Meniere's disease (CR-MD)and corticosteroid-resistant or intolerant autoimmune inner ear disease (CR-AIED) patients. Patients will be randomized by a 2:1 allocation to anakinra or placebo for 42 continuous days. After day 42, a second placebo-controlled period will begin for an additional 42 days. This will be followed by a 264 day observation period, during which, hearing declines may be re-treated with anakinra after 30 days following the initial drug.

Conditions

Autoimmune Inner Ear Disease; Meniere's Disease

Outcome Measures

Primary Outcomes (2)

• Sustained improvement in hearing thresholds

  Determine whether those treated with anakinra demonstrate a sustained improvement in hearing thresholds compared with their pre-anakinra treatment threshold. Improvement will be defined by an improvement of 15dB at 1 frequency or 10dB at 2 contiguous frequencies with no greater than a 5dB worsening all remaining frequencies

  Hearing improvement from pre-treatment thresholds at day 28

• Sustained improvement in hearing thresholds

  threshold. Improvement will be defined by an improvement of 15dB at 1 frequency or 10dB at 2 contiguous frequencies with no greater than a 5dB worsening all remaining frequencies

  Hearing improvement from pre-treatment thresholds at day 42

Secondary Outcomes (2)

• Improved Word Recognition

  at day 28

• Improved Word Recognition

  at day 42

Study Arms (3)

Group A

EXPERIMENTAL

This group will be randomized to receive intervention of 42 consecutive days of anakinra (100mg/0.67ml) in period 1 followed by an additional 42 consecutive days of anakinra (100mg/0.67ml) in period 2

Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 1); Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 2)

Group B

EXPERIMENTAL

This group will be randomized to receive intervention of 42 consecutive days of anakinra (100 mg/0.67ml) in period 1 followed by 42 consecutive days of placebo in period 2

Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 1); Drug: Placebo injection (Period 2)

Group C

EXPERIMENTAL

This group will be randomized to receive intervention of placebo for 42 consecutive days in period 1 followed by 42 consecutive days of anakinra (100mg/0.67ml) in period 2

Drug: Placebo injection (Period 1); Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 2)

Interventions

Placebo injection (Period 2) DRUG

pre-filled matching placebo injections will be provided and will be self-administered by patients daily during next 42 days of treatment (Period 2)

Group B

Anakinra 100Mg/0.67Ml Inj Syringe (Period 1) DRUG

pre-filled syringes of anakinra 100mg/0.67mg will be provided and will be self-administered by patients daily during first 42 days of treatment (Period 1)

Group A; Group B

Placebo injection (Period 1) DRUG

pre-filled matching placebo injections will be provided and will be self-administered by patients daily during first 42 days of treatment (Period 1)

Group C

Anakinra 100Mg/0.67Ml Inj Syringe (Period 2) DRUG

pre-filled syringes of anakinra 100mg/0.67mg will be provided and will be self-administered by patients daily during next 42 days of treatment (Period 2)

Group A; Group C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• meet diagnostic criteria for Autoimmune Inner Ear Disease (AIED) with active deterioration in one ear as defined below
• SNHL of greater than 30dB at one or more frequencies in the active ear. The contralateral ear may have any hearing threshold that is either stable or worsening, but may not exhibit improvement in response to corticosteroids even if the more active ear declines. Active deterioration is defined as a 15dB decline at one frequency (excluding 250 or 8kHz as a sole indicator) on their audiogram, or 10dB at 2+ frequencies developing in \> or equal 3 days but \< or equal 90 days, or if the hearing loss evolved in less than 3 days, the patient displayed features suggestive of an autoimmune disorder
• Capable of understanding and giving informed consent
• Have 2 sequential audiograms following the decline in hearing \>or equal 28 days apart with no demonstrable improvement in hearing following corticosteroid therapy (\<or equal 5dB of improvement at any individual frequency (250, 500, 1000, 2000 and 4000Hz) and \<12% improvement in WRS)
• Patients must have been treated with oral or IT prednisone with no demonstrable improvement or attempted to be treated and deemed intolerant. Steroid intolerance is defined as unable or unwilling to take corticosteroids because of a prior untoward effect or a current medical condition that would negatively be impacted by steroid use
• Must have completed steroid therapy, including any intratympanic steroid therapy
• Meniere's disease defined according to the AAO criteria, with the additional requirement of corticosteroid resistance AND no new diuretics may be instituted or dose increased from 28 days prior to trial enrollment
• Patients must be fluent in English as all word recognition scores are based on testing in English
• Patients may have other autoimmune disease(s) Females of childbearing potential, must be practicing a method of birth control considered effective and medically acceptable by the investigator for a minimum of 2 months prior to the study and at least 2 months after last administration of study drug
• Males similarly must be practicing a method of birth control considered effective and medically acceptable by the investigator for a minimum of 2 months prior to the study and at least 2 months after last administration of study drug

You may not qualify if:

• Evidence of retrocochlear pathology (vestibular schwannoma) or inner ear malformation (Mondini Malformation or Enlarged Vestibular Aqueduct) based on imaging
• Prior treatment with gentamicin for Meniere's Disease
• Most recent decline in hearing occurring \>90 days prior to trial enrollment
• Positive test for Muckle-Wells mutation
• Concurrently receiving methotrexate, TNF-antagonist therapy or any other immunosuppressive therapy
• Steroid-dependent hearing loss
• Any immunodeficiency syndrome
• Active or chronic infections
• Currently receiving, or having received treatment for a malignancy in the past 3 years
• Chronic renal insufficiency (a creatinine clearance of \<49mL/min) or chronic renal failure
• Neutropenia prior to treatment with anakinra
• Receipt of live vaccine \<3 months prior to enrollment
• Previous treatment with an IL-1 antagonist for any clinical indication
• First-degree relative with a diagnosis of a CAPS disease
• History of active narcotic abuts, including prescription narcotics

Sponsors & Collaborators

• Northwell Health: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (1)

Northwell Health, Hearing& Speech Center

New Hyde Park, New York, 11042, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 25133431 RESULT

• Pathak S, Goldofsky E, Vivas EX, Bonagura VR, Vambutas A. IL-1beta is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J Immunol. 2011 Feb 1;186(3):1870-9. doi: 10.4049/jimmunol.1002275. Epub 2011 Jan 3.

  PMID: 21199898 RESULT

MeSH Terms

Conditions

Meniere Disease

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Endolymphatic Hydrops; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Andrea Vambutas, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ginny Mullooly, RN

CONTACT

718-470-7974; gmullool@northwell.edu

Andrea Vambutas, MD

CONTACT

718-470-7550; avambuta@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The subject, investigator and study coordinator will all be blinded to the randomization assignment. Only the study pharmacist will be unblinded when dispensing the study medication
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a randomized, placebo-controlled design with a 2:1 allocation of anakinra or placebo for the first 42 continuous days. After day 42, a second placebo-controlled period will begin for an additional 42 days.

Study Record Dates

• First Submitted: June 12, 2018
• First Posted: July 16, 2018
• Study Start: January 3, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)