Treatment Interruption of Natalizumab

Study Overview
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Brief Summary
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This is a randomized, rater blinded trial in patients who interrupt treatment with natalizumab with or without being treated with other immunomodulatory drugs, or continue treatment with natalizumab. The main purpose of this study is to find out the following, when participants stop taking natalizumab for 24 weeks: when MS symptoms return, and if other drugs for MS may help control MS symptoms during the natalizumab-interruption period. This study will also explore how quickly the effects of natalizumab return after resuming natalizumab dosing.

Official Title
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Randomized Treatment Interruption of Natalizumab

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: natalizumab
* Drug: interferon beta 1-a
* Drug: methylprednisolone
* Other: IV placebo
* Drug: glatiramer acetate


Participation Criteria
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Eligibility Criteria
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Major criteria include: A diagnosis of a relapsing form of MS Treatment with natalizumab according to locally approved prescribing information Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: natalizumab<br> | Drug: natalizumab<br>* 300 mg intravenous every 4 weeks<br>|
| Placebo Comparator: IV placebo<br> | Other: IV placebo<br>* placebo intravenous every 4 weeks<br>|
| Active Comparator: interferon β-1a, glatiramer acetate, or methylprednisolone<br> | Drug: interferon beta 1-a<br>* 30 ug intramuscular once per week<br>Drug: methylprednisolone<br>* 1000 mg intravenous every 4 weeks<br>Drug: glatiramer acetate<br>* 20 mg subcutaneous once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria. | Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of >0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was >5.5 | 28 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | MRI rescue criteria were the presence of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size, according to the central MRI reader. | 28 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS