Zenapax to Treat Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title: Effect of the Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (IL-2R-Alpha; Zenapax(Registered Trademark)) on Inflammatory Activity in the CNS in MS in a Baseline-to-Treatment, Cross-Over, MRI-Controlled Single Center Phase I/II Trial

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

• NCT number: NCT00001934
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: September 1999
• Completion date: September 2008