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Effects of Anakinra in Subjects With Autoimmune Inner Ear Disease

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ClinicalTrials.gov Identifier: NCT03587701
Recruitment Status : Recruiting
First Posted : July 16, 2018
Last Update Posted : March 19, 2019
Sponsor:
Collaborator:
Sobi
Information provided by (Responsible Party):
Andrea Vambutas, Northwell Health

Brief Summary:
A Phase II randomized, placebo controlled study design of anakinra (Kineret) in autoimmune inner ear disease (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.

Condition or disease Intervention/treatment Phase
Autoimmune Inner Ear Disease Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 1) Drug: Placebo injection (Period 1) Drug: Anakinra 100Mg/0.67Ml Inj Syringe (Period 2) Drug: Placebo injection (Period 2) Phase 2

Detailed Description:
This study will be evaluating whether or not anakinra (kineret) is superior to placebo for improving sustained hearing thresholds in patients with AIED. Final enrollment is contingent on an acute decline in hearing in one or more ears and 2 sequential audiograms greater than or equal to 28 days apart that shows a stable or declining hearing threshold and word recognition score, with or without treatment. Patients may have been treated with oral prednisone or intratympanic steroids within 30 days prior to trial enrollment, regardless of corticosteroid response, as long as they meet enrollment criteria and have completed corticosteroid therapy by 14 days prior to study enrollment. Anakinra (kineret) 100mg/0.67ml prefilled syringes or placebo injection will be randomized at 2:1 allocation and will be self-administered by the patient daily for 42 days. After day 42, a second placebo-controlled period will begin for an additional 42 days (all patients will receive anakinra for either 42 or 84 days depending on the randomization assignment). A 264 day observation period will begin after day 84, during which the option to retreat with anakinra will be offered to those patients that responded to the therapy in the first 84 day period.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The subject, investigator and study coordinator will all be blinded to the randomization assignment. Only the study pharmacist will be unblended when dispensing the study medication
Primary Purpose: Treatment
Official Title: A Phase II Placebo Controlled Study of the Effects of Anakinra (Kineret) in Subjects With Autoimmune Inner Ear Disease Disease (AIED)
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ear Disorders
Drug Information available for: Anakinra

Arm Intervention/treatment
Experimental: Group A
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)
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)

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

Experimental: Group B
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)
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)

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

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

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




Primary Outcome Measures :
  1. Sustained improvement in hearing thresholds [ Time Frame: Hearing improvement from pre-treatment thresholds at day 28 ]
    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

  2. Sustained improvement in hearing thresholds [ Time Frame: Hearing improvement from pre-treatment thresholds at day 42 ]
    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


Secondary Outcome Measures :
  1. Improved Word Recognition [ Time Frame: at day 28 ]
    Determine whether those treated with anakinra demonstrate a sustained improvement in word recognition score compared with their pre-anakinra treatment threshold. Improvement will be defined by an improvement of greater than 12% change in value

  2. Improved Word Recognition [ Time Frame: at day 42 ]
    Determine whether those treated with anakinra demonstrate a sustained improvement in word recognition score compared with their pre-anakinra treatment threshold. Improvement will be defined by an improvement of greater than 12% change in value



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 both ears with evidence of active deterioration (elevated threshold) in at least one ear of 15dB 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 with or without therapeutic intervention (<or equal 5dB of improvement at any individual frequency (250-8kHz and <12% improvement in WRS)

    -> 14 days since any prior steroid usage

  • 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

Exclusion Criteria:

  • Evidence of retrocochlear pathology (vestibular schwannoma) or inner ear malformation (Mondini Malformation or Enlarged Vestibular Aqueduct) based on imaging
  • Meniere's Disease- Patients with episodic vertigo and fluctuating SNHL according to AAO-HNS diagnostic criteria for Meniere's disease are unlikely to have their symptoms on the basis of autoimmunity
  • Most recent decline in hearing occurring >60 days prior to trial enrollment
  • Positive test for Muckle-Wells mutation
  • Concurrently receiving methotrexate, TNF-antagonist therapy or any other immunosuppressive therapy
  • 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
  • Pregnant or lactating females
  • Non-English speaking patients
  • Seropositive 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
  • History of suicidal ideation, significant depression that resulted in hospitalization, or answers "yes" during C-SSR screening
  • Prior participation in any type of clinical trial using a medication that inhibits interleukin-1 activity
  • Known hypersensitivity to E.coli derived products
  • Latex sensitivity

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03587701


Contacts
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Contact: Ginny Mullooly, RN 718-470-7974 gmullool@northwell.edu
Contact: Andrea Vambutas, MD 718-470-7550 avambuta@northwell.edu

Locations
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United States, New York
Northwell Health, Hearing& Speech Center Recruiting
New Hyde Park, New York, United States, 11042
Contact: Andrea Vambutas, MD    718-470-7550    avambuta@northwell.edu   
Contact: Ginny Mullooly, RN    718-470-7974    gmullool@northwell.edu   
Sponsors and Collaborators
Northwell Health
Sobi
Investigators
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Principal Investigator: Andrea Vambutas, MD Northwell Health

Publications of Results:
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Responsible Party: Andrea Vambutas, M.D., Northwell Health
ClinicalTrials.gov Identifier: NCT03587701     History of Changes
Other Study ID Numbers: 18-0195
First Posted: July 16, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ear Diseases
Labyrinth Diseases
Labyrinthitis
Otorhinolaryngologic Diseases
Otitis
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents