A Double Blind, Placebo Controlled Multi-Center Pilot Study to Evaluate the Efficacy and Safety of MBP8298 in Relapsing Remitting Multiple Sclerosis

INTERVENTION: Product Name: MBP8298 Synthetic Peptide Product Code: MBP8298 Pharmaceutical Form: Powder for injection* CAS Number: 781666‐30‐6 Current Sponsor code: MBP8298 Other descriptive name: MBP8298 Synthetic Peptide Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intravenous use CONDITION: Relapsing Remitting Multiple Sclerosis INCLUSION CRITERIA: 1. Male or female subjects, 18‐50 years of age 2. Relapsing‐remitting multiple sclerosis (RRMS) according to “Diagnostic criteria for multiple sclerosis: 2005 revisions to the McDonald Criteria” (Annals of Neurology 58: 840‐846) 3. At least 2 years history of MS before trial entry 4. Documented history of 2 or more exacerbations in the 2 years prior to trial entry 5. Stable neurological status for at least 30 days before first study drug administration 6. Have an EDSS from 0‐5.5 7. If female, she must either ‐ be post‐menopausal or surgically sterilized; or ‐ use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and ‐ be neither pregnant nor breast‐feeding 8. Willingness and ability to comply with the protocol for the duration of the study 9. In the Investigator’s opinion, subjects must be reliable, compliant, and agree to cooperate with all t PRIMARY OUTCOME: Main Objective: The primary objective of this study is to demonstrate efficacy ‐ as measured with annualized relapse rate after 12 months treatment ‐ and safety of MBP8298 versus placebo in subjects diagnosed with RRMS and who are positive for HLA DR2/4 haplotypes. Primary end point(s): Primary efficacy endpoints:; The primary efficacy endpoint is the annualized relapse rate after 12 months of treatment.; The secondary efficacy endpoints:; A. Main Secondary endpoints; a. Clinical related endpoints; Disability related; Disability progression defined as the time to confirmed worsening of disability as measured by EDSS and MSFC at 12 24 and 27 months; Exacerbation (relapse) related; • Proportion of subjects relapse‐free at 12, 24 and 27 months ; b. MRI related endpoints; • Number of active lesions per subject per scan defined as new T1 gadolinium‐enhancing, or new T2 non‐enhancing or enlarging lesions at all MRI follow‐up visits (designated “combined unique activity”); • Number of active T2 lesions per subject per scan at the end of first and second year; • Number of active T1 gadolinium‐enhanced lesions per subject per scan at the end of first and second year; B. Other secondary endpoints (exploratory); a. Clinical related endpoints; Exacerbation (relapse) related; • Number of hospitalizations because of exacerbation at 12, 24 and 27 months; • Duration of exacerbations; • Severity of exacerbations as assessed with EDSS; • Time to first exacerbation; • Time to second exacerbation; • Time from first to second exacerbation; • Number of steroid courses for relapse treatment at 12, 24 and 27 months; • Proportion of DR2/4 +ve and DR2/4 –ve subjects in the RRMS population; Disability related; • Integrated disability status scale (IDSS = area under the EDSS curve above baseline value) at 12, 24 and 27 months ; • Time to disability progression; QOL ; • Functional Assessment of Multiple Sclerosis (FAMS) (Cella DF et al. 1996) at 6, 12, and 27 months; b. MRI related endpoints; • Proportion of subjects with no active T2 lesions at 12 and 24 months; • Proportion of subjects with no active T1 gadolinium‐enhanced lesions 12 and 24 months; • Change in T2‐weighted lesion volume 12 and 24 months; • Change in T1‐weighted hypointense lesion volume 12 and 24 months; • Brain volume change, as measured by MRI, 12 and 24 months; Secondary Objective: The secondary objective of this study is to assess efficacy and safety of MBP8298 versus placebo in subjects who are negative for HLA DR2/4 haplotypes and to assess in all subjects the time to confirmed worsening of disability as measured by EDSS and MSFC and the effects of MBP8298 on MRI parameters like; • Activity analysis (T2 lesions, Gadolinium enhancing lesions); • Lesion burden (T2 burden of disease, chronic T1 black holes); • Brain Atrophy