Difference in Efficacy of Natalizumab Versus Fingolimod for the Treatment of Multiple Sclerosis

NCT ID: NCT01981161

Last Updated: 2020-08-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 307 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-11-19
• Study Completion Date: 2018-11-30

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 .

Conditions

Multiple Sclerosis

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Fingolimod

patients treated by Fingolimod will have biological samples and clinical data

biological samples and clinical data

Intervention Type: PROCEDURE

Natalizumab

patients treated by Natalizumab will have biological samples and clinical data

biological samples and clinical data

Intervention Type: PROCEDURE

Interventions

biological samples and clinical data

Intervention Type: PROCEDURE

Eligibility 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Brassat, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

U H Toulouse

Locations

CHU Besançon

Besançon, , France

CHU Bordeaux

Bordeaux, , France

CHU Caen

Caen, , France

Chu Lille

Lille, , France

Chu La Timone

Marseille, , France

CHU Nancy

Nancy, , France

CHU Nantes

Nantes, , France

CHU Nice

Nice, , France

CHU Nîmes

Nîmes, , France

CHRU Strasbourg

Strasbourg, , France

Université de Muenter

Münster, , Germany

Hôpital Vall D'Hebron

Barcelona, , Spain

Countries

France; Germany; Spain

Other Identifiers

1235207

Identifier Type: -

Identifier Source: org_study_id