Towards Personalized Dosing of Natalizumab in Multiple Sclerosis

Phase 4

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: Natalizumab

• Registration Number: NCT03516526
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-11-03
• Study First Submitted: 2018-04-12
• Study First Submitted QC: 2018-04-23
• Study First Posted: 2018-05-04
• Primary Completion: 2019-06-21
• Status Verified: 2019-07
• Study Completion: 2019-07-01
• Last Update Submitted: 2019-07-11
• Last Update Posted: 2019-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All patients in this study	Natalizumab	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.

Primary Outcome Measures

Name	Time	Method
Gadolinium enhancing T1 lesions on brain MRI	12 months	Occurrence and number of gadolinium enhancing T1 lesions of brain MRI

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Rijnstate Hospital; 🇳🇱 Arnhem, Netherlands

St. Antonius Hospital; 🇳🇱 Utrecht, Netherlands

VU medical center; 🇳🇱 Amsterdam, Netherlands

Erasmus medical center; 🇳🇱 Rotterdam, Netherlands

OLVG; 🇳🇱 Amsterdam, Netherlands