Zenapax (Daclizumab) to Treat Relapsing Remitting Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine the safety of Zenapax (daclizumab) in patients with multiple
      sclerosis (MS). MS is thought to be caused by an over-reactive immune response. T-lymphocytes
      (cells of the immune system), are thought to damage myelin, a substance that covers the nerve
      and parts of the spinal cord and is damaged in patients with MS. Interleukin-2 is a natural
      substance in the body that is necessary for the growth of T-lymphocytes. Zenapax is a
      genetically engineered antibody that blocks the activity of interleukin-2 and thus interferes
      with the growth of lymphocytes. Therefore, Zenapax may prevent some of the damage to myelin
      that occurs in multiple sclerosis.

      Patients between 18 and 65 years of age with relapsing remitting MS may be eligible for this
      study. Patients with secondary-progressive or primary progressive MS may not participate.
      Candidates will be screened with a complete neurological and medical evaluation and review of
      medical records.

      Participants will undergo the following tests and procedures:

        -  Baseline evaluation: Participants have four magnetic resonance imaging (MRI) scans over
           a 3-month period to assess disease activity. For the MRI scans, the patient lies on a
           table that slides into the scanner - a narrow metal cylinder with a strong magnetic
           field. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between
           45 and 90 minutes. Only patients with activity at or above a certain level are eligible
           to continue with the treatment phase of the study.

        -  Zenapax treatment: Patients receive intravenous (through a vein) infusions of Zenapax.
           The first two infusions are 2 weeks apart, followed by 13 monthly infusions.

        -  MRI scans: Patients undergo MRI scanning before every infusion to evaluate disease
           activity and identify new brain lesions.

        -  Blood and urine tests: Blood and urine samples are collected at each clinic visit for
           routine laboratory evaluations, immunologic study, and genetic testing to determine a
           predisposition for responding to Zenapax treatment.

        -  Lumbar puncture (spinal tap): This procedure will be done during the last month before
           starting treatment and during the seventh month of treatment to examine immune changes
           that occur in the cerebrospinal fluid (CSF), which circulates through and surrounds the
           brain and spinal cord. A local anesthetic is given and a needle is inserted in the space
           between the bones in the lower back where the CSF circulates below the spinal cord. A
           small amount of fluid is collected through the needle.

        -  Skin test: A needle is placed just under the skin is done to assess the patient's immune
           status to common antigens such as tetanus, mumps and candida.

        -  Lymphocytopheresis: Lymphocytes are collected three times - once during the last month
           of baseline before starting treatment, once during the fifth month of treatment, and
           once during the last month of treatment - for immunologic study. Blood is collected
           through a needle in an arm vein in a similar way to donating blood. The blood flows from
           the vein through a catheter (plastic tube) into a machine that separates it into its
           components by centrifugation (spinning). The lymphocytes are removed and the rest of the
           blood (red cells, plasma and platelets) is returned to the body, either through the same
           needle or through another needle in the other arm.
    

Detailed description: 
      Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease leading to central
      nervous system (CNS) inflammation, demyelination, axonal loss, and leads to substantial
      disability in young adults. Existing approved treatments include interferon beta, glatiramer
      acetate and mitoxantrone. These therapies are only moderately effective in reducing disease
      activity.

      The Neuroimmunology Branch (NIB) has during the last three years tested the tolerability and
      safety of monthly intravenously administered daclizumab (Zenapax(Registered Trademark)), a
      humanized monoclonal antibody against the IL-2 receptor alpha chain, in patients who receive
      interferon-beta, but responded incompletely to therapy with interferon-beta. Daclizumab has
      been well tolerated and inhibited inflammatory disease activity by almost 90%. Under an
      amendment of this protocol, it was demonstrated that the efficacy of daclizumab is maintained
      once interferon-beta therapy is discontinued.

      In the current trial, we will test the efficacy of daclizumab alone in relapsing-remitting MS
      patients. This trial is a single-centre, open-label, baseline to treatment cross-over phase
      II trial. Daclizumab will be administered intravenously at 1mg/kg bodyweight.
      Contrast-enhancing MRI lesions will serve as the primary outcome measure in this phase II
      trial, and a number of clinical, MRI, and immunological parameters will be measured as
      secondary and tertiary outcomes. Daclizumab is a promising new immunomodulatory treatment for
      relapsing-remitting MS.
    

Intervention name(s): Daclizumab
Intervention type(s): Drug
Intervention MeSH terms: Daclizumab
Primary purpose: Treatment
Keywords: Neuroimmunology; Therapy; Demyelinating Disease; Immunological Mechanism; MRI; Multiple Sclerosis; MS