A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension

This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of
the placebo-controlled period (Part 1), participants will have the option of enrolling in a
2-year open-label extension (Part 2).

Part 1: The primary objective of the study is to investigate whether treatment with
natalizumab slows the accumulation of disability not related to relapses in participants with
secondary progressive multiple sclerosis (SPMS).

The secondary objectives of Part 1 of this study are to determine the proportion of
participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in
participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12),
the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab
on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical
(MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24
using magnetic resonance imaging (MRI) and the proportion of participants experiencing
progression of disability as measured by individual physical Expanded Disability Status Scale
(EDSS) system scores.

Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of
natalizumab in participants with SPMS.

The secondary objectives of Part 2 of the study are to investigate long-term disability
(based on clinical or participant-reported assessments) in participants with SPMS receiving
natalizumab treatment for approximately 4 years and to assess change in brain volume and T2
lesion volume.