Fingolimod Versus Dimethyl-fumarate in Multiple Sclerosis

• Status: Terminated
• Trial end date: 2019-10-30
• Target enrollment: 0
• Participant gender: All

Summary

This will be a 1:1 randomized open label trial. European and outside Europe centres will be involved. Aim of the project is to conduct a head-to-head comparison of effectiveness of two approved disease modifying treatments (DMTs) in patients with relapsing remitting multiple sclerosis (RRMS). The term effectiveness refers to efficacy in a real life setting: this is intended to be in fact the first pragmatic multi-centre randomised controlled trial to directly assess the effectiveness of the new oral agents approved for MS (fingolimod/FTY versus dimethyl-fumarate/DMF) on disease activity, disability progression, quality of life, functioning and symptoms. It will be a randomized trial taking place in clinical care setting and comparing existing therapies, any of which may constitute standard care for naive patients or sub optimal responders to first-line drugs. Post hoc analysis will also identify the better treatment strategy on the different patient subgroups. Patient overall disease experience will be considered for the first time as the most important outcome. In fact, in addition to classical "no evidence of disease activity" (NEDA), a new composite NEDA taking account also of patient point of view and quality of life, will be proposed. Finally,the specific effectiveness profile of the two DMTs will be addressed, by exploring comparative benefits on different outcomes (disease activity, disability progression, brain atrophy, quality of life, fatigue, psychiatric and cognitive symptoms, medication satisfaction).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
• Collaborators: Patient-Centered Outcomes Research Institute; Universita degli Studi di Genova
• Treatments: Dimethyl Fumarate; Fingolimod Hydrochloride

Criteria

Inclusion Criteria:

• Adult patients with RRMS eligible to be treated with both FTY and DMF. Patients eligible for enrolment are patients for whom both drugs can be prescribed, upon clinical judgement and local label indication.

• Patients must be able to sign and date a written informed consent prior to entering the study. Where the subject is unable to write, consent may be given and recorded through appropriate alternative means in the presence of at least one impartial witness. In that case, the witness shall sign and date the informed consent document.

• Women of child-bearing potential must have a negative serum pregnancy test before enrollment and must practice an effective method of birth control, in line with normal clinical practice recommendations.

Exclusion Criteria:

• any FTY/DMF contraindication, as for authorized indications or clinical judgment;

• present immunodeficiency syndrome (primary or secondary immune deficiency);

• abnormal lymphocyte count;

• severe chronic active infections or acute infections not resolved at the time of the enrolment;

• evidence of active tuberculosis (TB);

• history of either untreated or inadequately treated latent TB infection;

• progressive Multifocal Leukoencephalopathy, even if only suspected;

• active malignancies;

• severe liver impairment (Child-Pugh class C);

• macular edema;

• sieronegative for antibodies IgG anti-VZV;

• hypersensitivity to the active substances or to any of the excipients;

• cardiac contraindications to FTY (patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure (HF) requiring hospitalization or Class III/IV HF; history or presence of Mobitz Type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker);

• pregnancy or breastfeeding;

• concomitant treatment with any other approved or investigational DMTs or other prohibited treatments.