Towards Personalized Dosing of Natalizumab in Multiple Sclerosis

Study Overview
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Brief Summary
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A prospective clinical trial with the aim of maintaining drug efficacy of natalizumab while extending dose intervals guided by drug concentrations in patients with relapsing remitting multiple sclerosis.

Detailed Description
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Our main objective is to prove that extending dose intervals guided by natalizumab serum concentrations, will not result in radiological or clinical disease activity in completely stable RRMS patients treated with natalizumab. Adult patients with RRMS with no evident disease activity during the last 12 months of natalizumab infusions with a minimum treatment of 12 months wil be included. Before subsequent natalizumab infusions, serum concentrations will be evaluated. If the concentration exceeds 15μg/ml the dose interval will be extended with a week to a maximum of eight weeks. Patients will get regular brain MRI scans and clinical follow-up.

Official Title
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Towards Personalized Dosing of Natalizumab in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Natalizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsing-remitting multiple sclerosis (RRMS) according to the McDonald criteria, revised by Polman 2010 Natalizumab treatment for 12 months or longer at inclusion. An expanded disability status scale (EDSS) score of 0.0-6.0 at baseline. Natalizumab level of ≥15 μg/ml Written informed consent. Exclusion Criteria: Any MS disease activity (radiologically or clinically) during the last 12 months of natalizumab treatment. Unable to undergo frequent MRI. The use of other immunomodulatory medication other than natalizumab.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All patients in this study<br>Patients treated with natalizumab with a minimum of 1 year, without signs of disease activity (relapses, new T2 lesions on MRI) for a minimum of 1 year. | Drug: Natalizumab<br>* Extending dose intervals of natalizumab from 4 weeks to maximum of 8 weeks based on trough natalizumab concentrations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gadolinium enhancing T1 lesions on brain MRI | Occurrence and number of gadolinium enhancing T1 lesions of brain MRI | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New T2 lesions on brain MRI | Occurrence and number of new T2 lesions on brain MRI | 12 months | 
| Relapses | scoring MS exacerbations | 12 months | 
| EDSS | Expanded Disability Status Scale: clinical scoring of disability in MS patients | 12 months | 
| MSFC | Multiple Status Functional Composite: clinical scoring of disability in MS patients | baseline and 12 months | 
| patient perspective measured with the SF-36 | questionnaire: Short Form-36 | baseline and 12 months | 
| patient perspective measured with the MSIS-29 | questionnaire: Multiple Sclerosis Impact Scale-29 | baseline and 12 months | 

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