Zenapax to Treat Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine the safety and effectiveness of Zenapax (a laboratory-manufactured
      antibody) in treating multiple sclerosis. Multiple sclerosis may be caused by an abnormal
      immune response in which white blood cells called T lymphocytes attack the myelin sheath that
      covers nerves and parts of the spinal cord. Zenapax binds to protein receptors on
      lymphocytes, keeping them from interacting with interleukin-2, a substance necessary for
      their growth.

      Patients with multiple sclerosis who have had at least one relapse within 18 months of the
      start of the study and in whom interferon-beta treatment has not been successful may be
      considered for this study. There are two study phases: baseline and treatment. During the
      baseline phase, patients will have three magnetic resonance imaging (MRI) scans over 2 months
      to evaluate their disease activity. During treatment, patients will receive seven intravenous
      (I.V.) infusions of Zenapax in the clinic. The first two infusions will be given 2 weeks
      apart; the next five will be given once a month.

      Patients will have MRI scans before each infusion. The MRIs will be done using the standard
      procedure and again using a contrast agent, gadolinium, injected into a vein. Gadolinium
      helps identify new multiple sclerosis lesions in the brain. Blood and urine samples will be
      taken during each clinic visit. In addition, patients will have skin tests, similar to a
      tuberculin test, to evaluate immune status, and will be asked to undergo two lumbar punctures
      (spinal tap; these will be optional)-one before the treatment phase begins, and another when
      treatment is completed. Lymphocytes will also be collected from patients before, during and
      after treatment. The lymphocytes are obtained by a procedure called apheresis: about a pint
      of whole blood is drawn through a needle in the arm, the lymphocytes are separated out and
      removed by a machine, and the rest of the blood is returned through a needle in the other
      arm. These studies will hopefully allow conclusions about the safety of Zenapax in MS, but
      also address its effectiveness with respect to modifying the inflammatory activity in the
      brain of MS patients and inhibit autoimmune T lymphocytes that are involved in the disease
      process.

      ...
    

Detailed description: 
      Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous
      system (CNS) that preferentially affects young adults. While its etiology is unknown, current
      concepts assume that CD4+ helper T cells with specificity for components of the myelin sheath
      initiate the pathogenetic process. The activation and expansion of such autoreactive T cells
      involves the secretion of autocrine growth factors, particularly interleukin-2 (IL-2), and
      the concomitant expression of its receptor, IL-2R, on the surface of T cells. Since only
      activated T lymphocytes can migrate through the blood brain barrier into the CNS and induce
      the inflammatory process, blocking the IL-2R should have an impact on disease activity in MS.

      In this trial , a humanized antibody against the IL-2Ra subunit (Zenapax(Registered
      Trademark)) will be used to inhibit T cell activation in MS patients who have failed
      conventional therapy by interferon-b. We will focus on the latter group of patients, since a
      substantial number of patients on conventional therapy respond only partially or completely
      fail treatment after longer periods of time. Up to 10 patients fulfilling these criteria will
      be enrolled in this baseline-to-treatment, cross-over, MRI-controlled single-center phase
      I/II trial to assess the safety of Zenapax(Registered Trademark) treatment and, at the same
      time, examine the clinical course and particularly the inflammatory activity in the CNS by
      monthly magnetic resonance imaging (MRI). Furthermore, immunological studies will be
      performed in parallel to the trial in order to a) identify the impact of Zenapax(Registered
      Trademark) treatment on immune parameters that should be affected by the blocking of the
      IL-2R, and b) to improve our understanding of the relevance of activated autoreactive T
      lymphocytes in MS.
    

Intervention name(s): Zenapax
Intervention type(s): Drug
Intervention MeSH terms: Daclizumab
Primary purpose: Treatment
Keywords: Multiple Sclerosis; Immunotherapy; MRI