IMCY-0141 Safety and Efficacy in Multiple Sclerosis - ISEMIS Study

The Sample Size determined for this study is as follows: Phase I: A total of 12 patients (4 patients in each of 3 dose cohorts) are planned to be enrolled. The study sample size has been estimated as adequate to provide a reliable safety assessment of the tested doses. All primary, secondary and exploratory endpoints will be summarized by descriptive statistics (continuous variables) or frequency tables (categorical variables), by dose group and overall. Additional patients may be enrolled if requested by the IDMC (Independent Data Monitoring Committee). Phase II: The sample size estimation is based on the total cumulative number of CUAL observed on brain MRI scans from week 12 till week 36. The study sample size has been estimated as adequate to determine if any IMCY-0141 doses offer superior efficacy (as measured by CUAL) relative to placebo. Using the negative binomial model for CUAL, a maximum total of 150 patients are planned to be enrolled (including the 12 patients enrolled in phase I), with 30 patients randomized to each of five groups: * Placebo * IMCY-0141 dose 1 * IMCY-0141 dose 2 * IMCY-0141 dose 3 * DMF (open label) During the adaptive design phase (Phase IIa), a minimum of 40 patients will be enrolled (with 8 patients randomized to each of five groups) and analyzed along with the 12 phase I patients as detailed here: * Placebo: 8 patients * IMCY-0141 dose 1: 8 patients + 4 phase I patients * IMCY-0141 dose 2: 8 patients + 4 phase I patients * IMCY-0141 dose 3: 8 patients + 4 phase I patients * DMF (open label) : 8 patients During the Phase IIb part, up to 98 additional patients will be enrolled in order to get up to 150 patients spread over the groups selected for Phase IIb, with a maximum 30 patients randomized to DMF. These sample sizes are sufficient to deliver Type I errors less than 5% in our chosen null scenarios, and unconditional powers greater than 75% and conditional powers greater than 90% in our two alternative scenarios.