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

• ClinicalTrials.gov Identifier: NCT01981161
• Recruitment Status: Completed
• First Posted: November 11, 2013
• Last Update Posted: August 25, 2020
• Sponsor: University Hospital, Toulouse
• Collaborator: European Commission
• Information provided by (Responsible Party): University Hospital, Toulouse

Study Description

Brief Summary:

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 .

Condition or disease	Intervention/treatment
Multiple Sclerosis	Procedure: biological samples and clinical data

Study Design

• Study Type: Observational
• Actual Enrollment: 307 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: November 19, 2013
• Actual Primary Completion Date: June 20, 2018
• Actual Study Completion Date: November 30, 2018

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Disease free patients [ Time Frame: 1 year ]

Secondary Outcome Measures :

1. 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 [ Time Frame: 1 year ]

Biospecimen Retention:   Samples With DNA

urine and blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Multiple sclerosis

Criteria

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.

Contacts and Locations

Locations

France

CHU Besançon

Besancon, France, 25000

CHU Bordeaux

Bordeaux, France, 33 000

CHU Caen

Caen, France, 14033

Chu Lille

Lille, France, 59037

Chu La Timone

Marseille, France, 13385

CHU Nancy

Nancy, France, 54035

CHU Nantes

Nantes, France, 44093

CHU Nice

Nice, France, 06002

CHU Nîmes

Nimes, France, 30029

CHRU Strasbourg

Strasbourg, France, 67098

Germany

Université de Muenter

Munster, Germany

Spain

Hôpital Vall D'Hebron

Barcelone, Spain

Sponsors and Collaborators

University Hospital, Toulouse

European Commission

Investigators

• Principal Investigator: David Brassat, MD,PHD; U H Toulouse

More Information

• Responsible Party: University Hospital, Toulouse
• ClinicalTrials.gov Identifier: NCT01981161
• Other Study ID Numbers: 1235207
• First Posted: November 11, 2013
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by University Hospital, Toulouse:

progressive multifocal leucoencephalopathy; JC virus; Zoster infection

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases