Clinical Disease Activity With Long Term Natalizumab Treatment

Study Overview
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Brief Summary
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The primary objective of the study is to retrospectively investigate the proportion of participants free of new or enlarging fluid-attenuated inversion recovery (FLAIR) lesions over time in approximately 300 Relapsing-Remitting Multiple Sclerosis (RRMS) participants with regular MRI follow-up, who have received natalizumab ≥24 month from two different observational cohorts: 1) approximately 230 participants from the Czech Republic; and 2) approximately 70 participants from Belgium. The secondary objectives of this study are as follows: Brain volume change by various measures; Changes in the number and volume of magnetic resonance imaging (MRI) lesions; No evidence of disease activity (NEDA) with and without brain volume change.

Detailed Description
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Natalizumab will not be provided to participants by Biogen as a part of this study. Participants will remain on natalizumab therapy as prescribed by their physician.

Official Title
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MRI and Clinical Disease Activity in Patients Treated Long Term With Natalizumab

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: natalizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of RRMS. Continuous treatment with natalizumab of ≥24 months. In case of a treatment interruption from natalizumab ≥60 days after a total treatment period of ≥24 months, only the treatment prior to the interruption will be analyzed. Any data after this treatment interruption (even if the patient restarts natalizumab) will not be analyzed/collected. ≥1 MRI scan of sufficient quality for reliable measurement. Baseline MRI scan ≤6 month prior to natalizumab treatment acquired. ≥1 MRI scan of sufficient quality for reliable measurement taken while on natalizumab treatment for ≥6 months. EDSS ≤ 6.5. Key Exclusion Criteria: Anti-natalizumab antibody detection. Prior treatment with alemtuzumab. Prior treatment with mitoxantrone within 12 months of the first infusion of natalizumab. 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 |
| --- | --- |
| Czech Republic<br>Approximately 230 participants with RRMS receiving commercial natalizumab in Czech Republic | Drug: natalizumab<br>* Participants with RRMS receiving commercial natalizumab in Belgium and Czech Republic<br>* Other names: Tysabri;|
| Belgium<br>Approximately 70 participants with RRMS receiving commercial natalizumab in Belgium | Drug: natalizumab<br>* Participants with RRMS receiving commercial natalizumab in Belgium and Czech Republic<br>* Other names: Tysabri;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change over time in the number of participants free of new or enlarging FLAIR lesions | Lesions that are ≥5 mm per scan (slice thickness 3 mm) as assessed by semiautomatic lesion count (by the Icometrix algorithm). | Treatment years 3 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized brain volume change rate as assessed by % change in brain parenchymal fraction [BPF] |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Annualized brain volume change rate as assessed by percent brain volume change [PBVC] |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Annualized brain volume change rate as assessed by white matter [WM] and gray matter [GM] atrophy) |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Cumulative number of new ≥6-month confirmed T1-hypointense lesions |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Annualized T1-hypointense and FLAIR lesion volume change |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Cumulative percent change in T1-hypointense and FLAIR lesion volume |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Cumulative number of ≥6-month-confirmed T1-hypointense lesions arising from new on- treatment Gadolinium (Gd+)-enhancing lesions | No relapse and no ≥6-month confirmed Expanded Disability Status Scale (EDSS) progression and no new or enlarging FLAIR lesions and no new Gd+-enhancing lesions | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Number of total participants and 4-year completers with NEDA as measured by clinical measures | No relapse and no ≥6-month confirmed EDSS progression and no new or enlarging FLAIR lesions and no new Gd+-enhancing lesions, brain volume change rate as assessed by PBVC | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Number of total participants and 4-year completers with NEDA as measured by radiological measures | No new or enlarging FLAIR lesions and no new Gd+-enhancing lesions | Post long term treatment with natalizumab (>2 years) through Year 4 | 
| Number of participants with brain volume loss ≤0.2% and ≤0.4% |  | Post long term treatment with natalizumab (>2 years) through Year 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RRMS, MRI