Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis

The purpose of this study is to determine the safety and efficacy of natalizumab in the treatment of individuals who have been diagnosed with relapsing remitting multiple sclerosis (MS). It is hoped that natalizumab will prevent certain types of white blood cells from moving out of the bloodstream into organs, including the brain, that are being damaged by autoimmune disease (a disease in which the body's own immune system attacks certain organs). These white blood cells are thought to cause inflammation that can result in lesions (small areas of damage) in the brain. These lesions are thought to be the cause of relapses and disability in MS.

• Drug: Natalizumab
  Natalizumab 300 mg IV infusion, every 4 weeks, for up to 116 weeks.
  Other Name: Tysabri
• Drug: Placebo
  Placebo, IV infusion, every 4 weeks, for up to 116 weeks.

• Experimental: Group 1
  Natalizumab 300 mg, IV
  Intervention: Drug: Natalizumab
• Placebo Comparator: Group 2
  Placebo IV infusion
  Intervention: Drug: Placebo

• Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910.
• Balcer LJ, Galetta SL, Polman CH, Eggenberger E, Calabresi PA, Zhang A, Scanlon JV, Hyde R. Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab in relapsing MS. J Neurol Sci. 2012 Jul 15;318(1-2):119-24. doi: 10.1016/j.jns.2012.03.009. Epub 2012 Apr 21.

Inclusion Criteria:

• Diagnosis of MS, as defined by McDonald et al., criteria # 1-4 (McDonald et al., 2001)
• Between the ages of 18 and 50, inclusive.
• Baseline EDSS score between 0.0 and 5.0, inclusive.
• Have experienced at least one relapse within the 12 months prior to randomization.
• Cranial MRI scan demonstrating lesion(s) consistent with MS.
• Have given written informed consent to participate in the study.

Exclusion Criteria:

• Primary progressive, secondary progressive, or progressive relapsing MS.
• MS relapse has occurred,in the opinion of the investigator, within 50 days prior to randomization and/or the subject has not stabilized from a previous relapse.
• A clinically significant infectious illness within 30 days prior to randomization.
• History of, or abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal and/or other major disease, that in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent for 116 weeks.
• History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
• Unable to perform the Timed 25-foot Walk, 9HPT, and PASAT 3.
• Abnormal blood tests performed at the Screening Visit.