Safety and efficacy of amiselimod in relapsing multiple sclerosis (MOMENTUM): a randomised, double-blind, placebo-controlled phase 2 trial

Summary Background Patients with multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system with autoimmune pathogenesis, have shown partial response to a number of immunomodulating treatments, but the search for more effective, safe, and convenient therapeutic options continues. Amiselimod is an oral selective modulator of sphingosine 1-phosphate 1 (S1P1 ) receptor, which is being developed for the treatment of various autoimmune-mediated diseases. We assessed the safety and efficacy of amiselimod in patients with relapsing– remitting multiple sclerosis. Methods In this double-blind phase 2 trial, patients aged 18–60 years with active relapsing–remitting multiple sclerosis from 84 centres in Europe and Canada were randomly assigned (1:1:1:1) with an interactive web-response system to receive once daily oral amiselimod 0·1 mg, 0·2 mg, 0·4 mg, or placebo for 24 weeks. All study personnel, site personnel, investigators, and patients were masked to the treatment assignment during the study. The primary endpoint was the total number of gadolinium-enhanced T1-weighted lesions on monthly brain MRI scans from weeks 8 to 24. Analysis was done on the predefined evaluable population (all randomised patients who did not have any major protocol deviations, completed 24 weeks of treatment as planned, and had at least three valid post-dose MRI scans). This trial is registered with ClinicalTrials.gov , number NCT01742052. Findings Between Jan 31, 2013, and Dec 24, 2013, 536 patients were screened and 415 patients randomly assigned to amiselimod 0·1 mg (n=105), 0·2 mg (n=103), 0·4 mg (n=104), or placebo (n=103). The median total number of gadolinium-enhanced T1-weighted lesions from weeks 8 to 24 did not differ between the amiselimod 0·1 mg and placebo groups (median 1·6 lesions [range 0–132] in the placebo group vs 2·0 [0–105] in the 0·1 mg group [median difference 0·0, 95% CI −1·0 to 0·0, p=0·7517]), but was significantly lower in the two higher amiselimod dose groups than in the placebo group (0·0 lesions [range 0–35] in the 0·2 mg group [median difference vs placebo −1·0, 95% CI −1·0 to 0·0, p=0·0021] and 0·0 [range 0–30] in the 0·4 mg group [–1·0, −1·2 to 0·0, p=0·0003]). The estimated incident rate ratio compared with placebo was dose-dependently decreased with amiselimod (0·1 mg 0·53 [95% CI 0·33–0·85; p=0·0079], 0·2 mg 0·39 [95% CI 0·24–0·63; p=0·0001], and 0·4 mg 0·23 [95% CI 0·14–0·38; p