Clinical Research Directory

A Prospective Randomized Non-inferiority Trial Comparing Anti-CD20 Maintenance Versus De-Escalation Strategy In Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS), the main central nervous system autoimmune disorder, is the first cause of non-traumatic disability in young adults and has thus significant individual consequences with elevated public health cost. It commonly starts during the third and fourth decades. Over the last twenty years, several disease-modifying therapies with variable benefit/risk profiles have been introduced leading to dramatic changes in the prognosis of MS. First, several moderately effective therapies , with good safety profile, have allowed to decrease the frequency of relapses along with a possible, albeit limited, effect on medium- and long-term disability. More recently highly effective therapies (HET), with immunosuppressive properties, have dramatically reduced clinical and MRI disease activity and significantly improved patient's prognosis. Anti-CD20 therapies (B-cells depleting therapies, given either intravenous or subcutaneous), one of the main HET, have demonstrated higher efficacy than platform therapies in several phase 3 randomized clinical trials and their use within the very first years of the disease seems to be associated with improved long-term outcomes. Taking all of this into account, the investigators hypothesize that RRMS patients who experience a de-escalation from anti-CD20 therapies to platform therapies after 40 years will not experience disease activity accrual and disability worsening.

MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS)

This is a Phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 (vidofludimus calcium), a small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), 30 mg/day and 45 mg/day in the main study, cohort 1 (and 10 mg/day for the patients in the cohort 2 substudy), in patients with RRMS and evidence of active disease. The trial consists of a screening period, a blinded 24-week main treatment period, and an optional initially blinded, then open-label extended treatment period of up to 9.5 years. About 40 centers are planned to participate in Romania, Bulgaria, Ukraine, and Poland; potential additional centers in Hungary and Croatia were not used. The study started with 195 patients in the main group (cohort 1) planned to be randomized 1:1:1 to treatment with 30 mg/day or 45 mg/day IMU-838, or placebo (65 patients each) in the main treatment period. During the extended treatment period, patients were initially re-randomized so that patients previously on placebo were re-randomized 1:1 to treatment with 30 g/day or 45 mg/day IMU-838, all other patients were re-randomized to the same treatment they previously received. With approval of Protocol Version 3.0, a sub-study patient group (cohort 2) has been added with up to 60 patients, randomized to placebo or 10 mg IMU-838 for 24 weeks after which the option is available to continue into the extended treatment period and the recommended dose of 30 mg/day. However, based on discussion between investigator and patient 45 mg/day IMU-838/day may also be used.