A multicenter, randomized, rater-blind study to compare the efficacy and safety of natalizumab (300 mg IV every four weeks) with Interferon beta-1a (44 mcg SC three times a week) in subjects with relapsing multiple sclerosis previously treated with Interferon beta-1a (22 or 44 mcg SC three times a week).

INTERVENTION: Product Name: Natalizumab Product Code: Not Applicable Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: natalizumab Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 20‐ Trade Name: Rebif 44 micrograms Product Name: Rebif 44 micrograms Pharmaceutical Form: Solution for injection INN or Proposed INN: Interferon beta‐1a Concentration unit: µg microgram(s) Concentration type: equal Concentration number: 44‐ CONDITION: Male and female subjects with relapsing multiple sclerosis previously treated with interferon beta‐1a (22 mcg or 44 mcg, SC three times a week). PRIMARY OUTCOME: Main Objective: The primary objective of this study is to compare the effect of natalizumab with IFN beta‐1a on the annualized rate of clinical relapses at 1 year. Primary end point(s): The primary endpoint of this study is to compare the effect of natalizumab with IFN beta‐1a on:; · Annualized clinical relapse rate ; ; The secondary objectives of this study are to compare the effect of natalizumab with IFN beta‐1a on:; ; · Probability of remaining relapse free; · Time to first relapse; · T2 activity on brain MRI scans; · Safety and tolerability; · Quality of Life; Secondary Objective: Secondary objectives include evaluation of the relative efficacy of natalizumab with IFN beta‐1a on other relapse and MRI outcomes.; ; The safety, tolerability and relative effects of natalizumab and IFN beta‐1a on quality of life will alsobe assessed. INCLUSION CRITERIA: Male and female subjects between 18 and 55 years of age who have a diagnosis of multiple sclerosis (MS) as defined by McDonald et al., criteria #1‐4 (McDonald et al., 2001, Section 22), and a baseline EDSS score between 0.0 and 5.5, inclusive. Randomized patients must have been treated with IFN beta‐1a at either 22 or 44 mcg SC three times a week (TIW) for at least 9 months prior to randomization and must have experienced at least one medically documented clinical relapse on IFN beta‐1a therapy within the 24 months prior to randomisation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range