Tysabri Observational Program (TOP)

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment
Relapsing-Remitting Multiple Sclerosis	Drug: natalizumab

Detailed Description:

TOP is an epidemiological observational study of participants receiving natalizumab, with each participant to be followed for up to 10 years. This study is designed to address the long-term safety profile and the long-term impact on disease activity and progression of natalizumab with marketed use, and the impact of treatment on disability in particular by comparing the results with prospectively determined controls from established databases.

Study Design

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Study Type :	Observational
Estimated Enrollment :	6000 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	TOP: Tysabri® Observational Program
Actual Study Start Date :	June 29, 2007
Estimated Primary Completion Date :	December 31, 2027
Estimated Study Completion Date :	December 31, 2027

Groups and Cohorts

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Group/Cohort	Intervention/treatment
natalizumab; According to the local prescribing information	Drug: natalizumab; According to the local prescribing information; Other Names: Tysabri; BG00002

Outcome Measures

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Primary Outcome Measures :

1. Number of participants with serious adverse events (SAE) [ Time Frame: Up to 10 years ]

Secondary Outcome Measures :

1. Annualized Relapse Rate (ARR) [ Time Frame: Yearly for up to 10 years ]
   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.
2. Distribution of the total number of relapses [ Time Frame: Yearly for up to 10 years ]
3. Time to first relapse [ Time Frame: Yearly for up to 10 years ]
4. Percentage of participants with relapse [ Time Frame: Yearly for up to 10 years ]
5. Percentage of participants with disability progression [ Time Frame: Yearly for up to 10 years ]
   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.
6. Percentage of participants that reach Expanded Disability Status Score (EDSS) milestones indicating increasing disability [ Time Frame: Yearly for up to 10 years ]
   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.
7. Percentage of participants whose EDSS worsened, stabilized or improved and sustained over 6 months [ Time Frame: Yearly for up to 10 years ]
8. Evaluation of baseline disease characteristics as prognostic indicators for disease activity and disability progression over time [ Time Frame: Yearly for up to 10 years ]
   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.
9. Evaluation of short-term (1 year) disease outcomes as prognostic indicators for disease activity and disability progression over time [ Time Frame: Yearly for up to 10 years ]
   Short term outcomes evaluated will include: EDSS progression during first 12 months; Occurrence of relapses during first 12 months

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Participants with RRMS who are therapy-naïve to natalizumab and who meet the criteria defined in the indication statement for prescription in the respective country.

Criteria

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-natalizumab 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.

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Biogen		clinicaltrials@biogen.com

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Sponsors and Collaborators

Biogen

Investigators

Study Director:	Medical Director	Biogen

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

TOP eDCT 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S; TYSABRI Observational Program (TOP) Investigators. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1190-7. doi: 10.1136/jnnp-2013-306936. Epub 2014 Feb 14.

Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT00493298 History of Changes
Other Study ID Numbers:	IMA-06-02
First Posted:	June 28, 2007
Last Update Posted:	April 4, 2018
Last Verified:	April 2018

Keywords provided by Biogen:

disease progression; Multiple Sclerosis; disease activity	Tysabri; natalizumab; long-term safety

Additional relevant MeSH terms:

Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases	Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Natalizumab; Immunologic Factors; Physiological Effects of Drugs