biogen/studies/attachments/NCT00493298-LLS.pdf

NCT00493298-LLS

The primary objective of this study is to assess the long-term safety and impact on
disease activity and progression of Tysabri in participants with relapsing remitting
multiple sclerosis (RRMS) in a clinical practice setting.

Tysabri Observational Program

Relapsing Remitting Multiple Sclerosis (RRMS)

Relapsing Forms of Multiple Sclerosis

RRMS

Multiple Sclerosis

TOP is an epidemiological observational study of participants receiving natalizumab, with
each participant to be followed for up to 15 years. This study is designed to address the
long-term safety profile and the long-term impact on disease activity and progression of
Tysabri with marketed use, and the impact of treatment on disability in particular by
comparing the results with prospectively determined controls from established databases.

TYSABRI

TOP: TYSABRI Observational Program

A clinical relapse is defined as new or recurrent neurological symptoms, not associated
with fever, lasting for at least 24 hours, and followed by a period of 30 days of
stability or improvement. New or recurrent neurological symptoms that occur less than 30
days following the onset of a protocol-defined relapse should be considered part of the
same relapse.

Disability progression is defined as at least a 1.0 point increase on the Expanded
Disability Status Scale (EDSS) from Baseline that is sustained over 6 months. The EDSS
measures disability status on a scale ranging from 0 to 10, with higher scores indicating
more disability. Scoring is based on measures of impairment in eight functional systems
on examination by a neurologist.

The percentage of participants that reach EDSS milestones such as 4.0, 6.0, and 7.0
sustained after 6 months. The EDSS measures disability status on a scale ranging from 0
to 10, with higher scores indicating more disability. Scoring is based on measures of
impairment in eight functional systems on examination by a neurologist.

Baseline disease characteristics evaluated will include: EDSS; Disease duration at
baseline; Number of relapses during 1 and 2 years before baseline; Previous use of
disease modifying therapy; Age, gender.

Short term outcomes evaluated will include: EDSS progression during first 12 months;
Occurrence of relapses during first 12 months

According to the local prescribing information

TYSABRI®

Relapsing-Remitting Multiple Sclerosis

The primary objective of this study is to assess the long-term safety and impact on disease
      activity and progression of Tysabri in participants with relapsing remitting multiple
      sclerosis (RRMS) in a clinical practice setting.

TOP is an epidemiological observational study of participants receiving natalizumab, with
      each participant to be followed for up to 15 years. This study is designed to address the
      long-term safety profile and the long-term impact on disease activity and progression of
      Tysabri with marketed use, and the impact of treatment on disability in particular by
      comparing the results with prospectively determined controls from established databases.

Research Site

Research site

A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. New or recurrent neurological symptoms that occur less than 30 days following the onset of a protocol-defined relapse should be considered part of the same relapse.

Disability progression is defined as at least a 1.0 point increase on the Expanded Disability Status Scale (EDSS) from Baseline that is sustained over 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.

The percentage of participants that reach EDSS milestones such as 4.0, 6.0, and 7.0 sustained after 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.

Baseline disease characteristics evaluated will include: EDSS; Disease duration at baseline; Number of relapses during 1 and 2 years before baseline; Previous use of disease modifying therapy; Age, gender.

Short term outcomes evaluated will include: EDSS progression during first 12 months; Occurrence of relapses during first 12 months