Tysabri Observational Program

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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TOP: TYSABRI Observational Program

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Tysabri


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented diagnosis of Relapsing Remitting Multiple Sclerosis The decision to treat with Tysabri must precede enrollment Patient must be a new Tysabri user, and must not have had more than 3 Tysabri infusions prior to enrollment Must have had at least one relapse in the previous year, and must satisfy locally approved therapeutic indications for Tysabri Key Exclusion Criteria: History of Progressive Multifocal Leukoencephalopathy or other opportunistic infections, or an increased risk of opportunistic infections History of positive anti-Tysabri antibodies Concomitant Immunomodulatory or immunosuppressive therapy during therapy with Tysabri Patient immunocompromised at the time of enrollment Known active malignancy Women must not be breast feeding or pregnant, or planning to become pregnant (must use birth control unless surgically sterile) NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tysabri<br>According to the local prescribing information | Drug: Tysabri<br>* According to the local prescribing information<br>* Other names: natalizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious Adverse Events (SAE) |  | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Relapse Rate (ARR) | 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. | Yearly for up to 15 years | 
| Distribution of the Total Number of Relapses |  | Yearly for up to 15 years | 
| Time to First Relapse |  | Yearly for up to 15 years | 
| Percentage of Participants with Relapse |  | Yearly for up to 15 years | 
| Percentage of Participants with Disability Progression | 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. | Yearly for up to 15 years | 
| Percentage of Participants that reach Expanded Disability Status Score (EDSS) Milestones Indicating Increasing Disability | 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. | Yearly for up to 15 years | 
| Percentage of Participants whose EDSS Worsened, Stabilized or Improved and Sustained over 6 Months |  | Yearly for up to 15 years | 
| Evaluation of Baseline Disease Characteristics as Prognostic Indicators for Disease Activity and Disability Progression Over Time | 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. | Yearly for up to 15 years | 
| Evaluation of Short-Term (1 year) Disease Outcomes as Prognostic Indicators for Disease Activity and Disability Progression Over Time | Short term outcomes evaluated will include: EDSS progression during first 12 months; Occurrence of relapses during first 12 months | Yearly for up to 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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disease progression, Multiple Sclerosis, disease activity, Tysabri, natalizumab, long-term safety