Difference in Efficacy of Natalizumab Versus Fingolimod for the Treatment of Multiple Sclerosis (BEST-MS)

Essai de Phase IV, Multicentrique, Ouvert, Visant à Tester la différence d'efficacité du Natalizumab, Versus le Fingolimod, 2 médicaments Ayant Une AMM Pour le Traitement de la sclérose en Plaques

Under the escalation treatment strategy when a patient displays breakthrough disease parameters under first line therapy, MS physicians are allowed by the EMEA to switch for Natalizumab (NTZ) or fingolimod (FGL). NTZ and FGL efficacy have been demonstrated by randomized therapeutic trial. As both treatments have been tested versus placebo a common way to compare them is to look at their respective annualized relapse risk ratio decrease. Roughly NTZ decrease by 70% and FGL by 50%. Nevertheless it is a terrible comparison since the placebo group had different behaviour in the 2 trials and the patients demographic features at baseline are also different. Therefore, it is right now totally impossible to compare these 2 drugs with a decent methodology. Only a head-to-head comparison could do it. Unfortunately this head-to-head comparison is not available and will not probably be done under the drug companies initiative. During the time of this study, we will perform a phase IV, observational, prospective head-to-head comparison of NTZ versus FGL efficacy in 600 patients. Our primary end point will be disease free patients after 1 year of treatment. Further, this trial will allow us to collect new biological samples, useful for a validation our project main aim. Further these new samples will be obtained from 3 European countries, which is a must if we want to generalize our conclusion obtained from a French cohort. Cooperation at the European level is thus essential for the implementation of this project .

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Procedure: biological samples and clinical data

• Study Type: Observational
• Enrollment (Actual): 307

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25000
    • CHU Besançon
  • Bordeaux, France, 33 000
    • CHU Bordeaux
  • Caen, France, 14033
    • CHU Caen
  • Lille, France, 59037
    • CHU Lille
  • Marseille, France, 13385
    • CHU La Timone
  • Nancy, France, 54035
    • CHU Nancy
  • Nantes, France, 44093
    • CHU Nantes
  • Nice, France, 06002
    • CHU NICE
  • Nimes, France, 30029
    • CHU Nimes
  • Strasbourg, France, 67098
    • CHRU Strasbourg
• Germany
  • Munster, Germany
    • Université de Muenter
• Spain
  • Barcelone, Spain
    • Hôpital Vall D'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Multiple sclerosis

Description

Inclusion Criteria:

• diagnosis of relapsing-remitting MS in line with McDonald criteria;

• patient needing to be treated with FGL or NTZ, either:

  • Patients who have not responded to complete and well-conducted treatment with beta interferon. The patients should have presented at least one relapse during the course of the previous year while they were receiving treatment, and should present at least 9 hyper-intense lesions within T2 on a cerebral MRI, or at least 1 enhancing lesion following injection of Gadolinium; or
  • Patients presenting severe and rapidly developing relapsing-remitting multiple sclerosis, defined by 2 debilitating relapses or more during the course of one year, combined with 1 or more high-intensity lesion(s) following injection of Gadolinium on a cerebral MRI, or a significant increase in lesion load within T2 compared to a recent prior MRI.
• EDSS score between 0 and 6, not inclusive;
• patient who give informed consent, and signed the consent form;
• patient available for 12-month follow-up.

Exclusion Criteria:

• General exclusion criteria: The patient is subject to judicial protection, supervision or guardianship, the patient is pregnant, is about to give birth, or is breast-feeding, or there is an existing medical or major psychiatric condition that, in the investigator's opinion, could represent a risk for the subject or could compromise compliance with the study protocol.
• Contraindication to the use of NTZ and FGL in line with the marketing authorisation: for NTZ, the risk of tuberculosis assessed by means of intracutaneous reaction or quantiferon dosage, for FGL, positive VZV serology and an absence of risk factors for bradycardia and heart rate problems, and for both molecules, an absence of biological signs suggesting immunodepression (negative HIV serology, normal CD3, CD4, CD8 and CD19 levels, weight-adjusted dosage of immunoglobulin normal).
• prior treatment with FGL or NTZ;
• prior treatment with Mitoxantrone or Cyclophosphamide type immunosuppressants during the 5 years before inclusion.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fingolimod; patients treated by Fingolimod will have biological samples and clinical data	Procedure: biological samples and clinical data
Natalizumab; patients treated by Natalizumab will have biological samples and clinical data	Procedure: biological samples and clinical data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free patients	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
comparing the efficacy of Natalizumab with that of Fingolimod with regard to the annual incidence rate (comparison against the annual incidence rate criterion after 1 year	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: European Commission
• Investigators: Principal Investigator: David Brassat, MD,PHD, U H Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2013
• Primary Completion (Actual): June 20, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimate): November 11, 2013

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: JC virus; progressive multifocal leucoencephalopathy; Zoster infection
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 1235207

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED