Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      Multiple sclerosis (MS) is a disease of the central nervous system (CNS). People who have MS
      may have lesions that form on parts of the CNS, such as the brain. Some of these lesions may
      be inflamed for a long time. This causes MS to progress. There is no treatment for these
      lesions. Researchers believe that a drug that decreases inflammation can help.

      Objective:

      To see if a drug called anakinra can help clear inflammation in MS brain lesions.

      Eligibility:

      People 18 and older with MS and at least one white matter lesion.

      Design:

      Participants will be screened with one or more Neuroimmunology Clinic protocols.

      Participants will have a medical history and physical exam. They will have blood and urine
      tests. They will have a lumbar puncture. For this, a needle is inserted between the bones in
      the back, and cerebrospinal fluid is removed. They will also have an MRI of the brain. The
      MRI scanner is a cylinder surrounded by a strong magnetic field. Participants will lie on a
      table that slides in and out of the scanner.

      Participants will repeat the above procedures throughout the study.

      Participants will get their first dose of anakinra at the clinic. They will administer the
      rest of the doses themselves, by injection under the skin.

      Participants will track their daily dosage electronically or in a written drug diary.

      Participants will have 4 visits while taking the drug. At each visit, sharps boxes and empty
      vials will be collected.

      Participants will have 2 follow-up visits after completing treatment.

      The study will last 28 weeks.
    

Detailed description: 
      Objective:

      The overall goal of this study is to determine the safety, tolerability, and radiological
      efficacy of up to 12 weeks of subcutaneous injection of anakinra in people with multiple
      sclerosis and evidence, by magnetic resonance imaging (MRI), of chronic active (also known as
      smoldering ) lesions in the white matter.

      Study population:

      5 people with progressive or stable MS, at least one paramagnetic rim lesion on 7-tesla MRI,
      and no new white matter lesion formation for at least 3 months or clinical relapse for at
      least 12 months, will complete the study.

      Design:

      In this open label, dose escalation study, participants will receive up to 12 weeks of

      subcutaneous anakinra with initial dose of 100 mg daily up to a target dose of 300 mg daily.
      Study visits will occur every 4 weeks while on treatment, with 2 follow-up visits at 4 and 12
      weeks after treatment discontinuation.

      Outcome measures:

      The primary outcome measure is disappearance of one or more paramagnetic rims from white
      matter lesions identified at baseline. Secondary outcomes include safety and tolerability,
      clinical and radiological outcomes. Exploratory serological and CSF measures will also be
      obtained to investigate mechanism of action of anakinra and for biomarker development.
    

Intervention name(s): Anakinra
Intervention type(s): Drug
Intervention description(s): 100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12.
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Active Lesions; Ultra-high-field (7T) MRI; Interleukin-1 (IL-1); White Matter; Paramagnetic Rim