Subcutaneous Ofatumumab in Relapsing Remitting Multiple Sclerosis

INTERVENTION: Trade Name: Arzerra Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: OFATUMUMAB CAS Number: 679818‐59‐8 Current Sponsor code: GSK1841157 Other descriptive name: NA Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: Relapsing‐Remitting Multiple Sclerosis (RRMS). ; MedDRA version: 14.1 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: To determine whether ofatumumab 3, 30 or 60 milligrams (mg) given subcutaneously (SQ), reduces the cumulative number of new T1 GdE brain lesions over a period of 12 weeks, as compared with placebo, in subjects with RRMS. Primary end point(s): Cumulative number of new T1 gadolinium‐enhancing brain lesions at Week 12 from Week 0 based on MRI scans at Weeks 4, 8, and 12 Secondary Objective: To evaluate the robustness of the MRI efficacy of ofatumumab 3, 30 or 60 milligrams (mg) given subcutaneously (SQ) over the 24 week treatment period relative to the first 12 weeks of the treatment period • To evaluate the safety and tolerability over a period of 24 weeks of a range of SQ ofatumumab doses in subjects with RRMS • To make a preliminary assessment of the efficacy of a range of SQ doses of ofatumumab in subjects with RRMS based on frequency of clinical relapses over a period of 24 weeks • To determine the extent of B‐cell depletion for a range of SQ doses of ofatumumab in subjects with RRMS • To determine the extent of B‐cell repletion following cessation of SQ ofatumumab treatment within specified time periods in subjects with RRMS • To evaluate the immunogenicity of SQ ofatumumab in subjects with RRMS For other study objectives please refer page12 of protocol. Timepoint(s) of evaluation of this end point: week 12 SECONDARY OUTCOME: Secondary end point(s): •Cumulative number of new T1 Gd‐enhancing brain lesions at Week 24 from Week 0 based on MRI scans at Weeks 4, 8, 12, 16, 20, and 24. •Gd‐enhancing brain lesions on T1‐weighted MRI based on MRI scans at Weeks 4, 8, and 12: ‐Cumulative number of persistent lesions at Week 12 from Week 0; ‐Cumulative number of all lesions at Week 12 (new plus persistent) from Week 0; ‐Total volume of new lesions at Week 12 (relative to Week 0); ‐Total volume of all lesions (new plus persistent) •T2 lesions based on MRI scans from Week 0 to Weeks 4, 8, and 12: ‐Cumulative number of new and/or newly enlarging lesions at Week 12; ‐Volume of new and/or newly enlarging T2 lesions at Week 12 •T1 hypointense lesions: ‐Cumulative number of new T1 hypointense lesions at Week 24 and Week 48 from Week 0; ‐Change from baseline in volume of T1 hypointense lesions at Week 24 and Week 48 •Change from baseline in brain volume at Week 24 and Week 48. Timepoint(s) of evaluation of this end point: Week 12, Week 24, and/or Week 48 INCLUSION CRITERIA: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Able to provide signed, written informed consent to participate in the study 2. 18‐55 years of age. 3. Definite diagnosis of MS according to the 2010 revisions of the McDonald diagnostic criteria for MS [Polman, 2011]. 4. Subjects do not have any manifestation of another type of MS other than RRMS. 5. Subjects must have a relapsing‐remitting course of disease with at least one of the following prior to screening: A. At least one confirmed relapse within the previous year or B. At least two confirmed relapses within the previous 2 years or C. At least one relapse in the previous 2 years, with a GdE brain lesion on an MRI scan in the past year. 6. Expanded Disability Status Scale (EDSS) score of 0‐5.5 (inclusive) at screening. 7. Neurologically stable with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase (subjects who relap