The MIRROR Study: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Investigate the Safety and MRI Efficacy of Subcutaneous Ofatumumab in Subjects with Relapsing-Remitting Multiple Sclerosis (RRMS) (S23.006)

OBJECTIVE: To determine the effects of distinct ofatumumab dosing regimens compared to placebo on cumulative number of new brain lesions assessed every 4 weeks for 12 weeks. BACKGROUND: Benefits of anti-CD20 monoclonal antibody infusions have been demonstrated in RRMS. We investigated the safety and efficacy of four subcutaneous ofatumumab dosing regimens in RRMS patients. DESIGN/METHODS: 232 subjects were randomized to one of 5 treatment groups: placebo, ofatumumab 3mg q12w, ofatumumab 30mg q12w, ofatumumab 60mg q12w, or ofatumumab 60mg q4w. Half of the subjects randomized to each of the 30mg and 60mg groups received a single initial 3mg dose at Week 0; all subjects were administered the first full dose at Week 1. At Week 12, placebo-randomized patients received a single 3mg ofatumumab dose. All subjects continued in the study for 24 weeks of treatment and in follow-up until B cell repletion. RESULTS: Weeks 0-12 data analysis estimated 65% reductions compared to placebo in the cumulative number of new T1 gadolinium-enhancing lesions for each ofatumumab dose regimen [p 90% reductions for each dose 蠅 30mg [p < 0.001]. A dose dependent CD19 B cell depletion across regimens and repletion seen with q12 week but not q4 week dosing was observed; rate of repletion of B cells following cessation of dosing was similar, with a delay of approximately 4 weeks in the 60mg q4 week group. The most common adverse events during Weeks 0-12 were injection-related reactions (52% of ofatumumab-treated subjects; 15% of placebo). Five serious adverse events were reported during treatment; all had received a 60mg dose regimen of ofatumumab; no cases of PML or opportunistic infections were observed. CONCLUSIONS: These results support further study of ofatumumab in longer studies of clinical efficacy in subjects with RRMS. Study Supported by: GlaxoSmithKline Disclosure: Dr. Bar-Or has received personal compensation for activities with Amplimmune, Aventis, Bayhill Therapeutics, Berlex/Bayer, Biogen Idec, BioMS, Diogenix, Eli Lilly & Company, EMD Serono, Genentech, Inc., Genzyme, GlaxoSmithKline, Inc., Guthy-Jackson/GGF, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Wyeth Pharmaceuticals. Dr. Bar-Or has received research support from Amplimmune, EMD Serono, and Novartis. Dr. Grove has received personal compensation for activities with GlaxoSmithKline Inc. as an employee. Dr. Austin has received personal compensation for activities with GlaxoSmithKlyne Inc. as an employee. Dr. Tolson has received personal compensation for activities with GlaxoSmithKline Inc. as an employee. Dr Tolson holds stock and/or stock options in GlaxoSmithKline Inc. Dr. VanMeter has received personal compensation for activities with GlaxoSmithKline Inc. as an employee. Dr. VanMeter holds stock in GlaxoSmithKline Inc. Dr. VanMeter has received research support from GlaxoSmithKline Inc. Dr. Lewis has received personal compensation for activities with GlaxoSmithKline Inc. as an employee. Dr. Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, Teva Neuroscience, Elan Corp., and GlaxoSmithKline Inc. Dr. Sorensen has received personal compensation in an editorial capacity for the European Journal of Neurology, Multiple Sclerosis Journal, and Therapeutic Advances in Neurological Disorders. Dr. Sorensen has received research support from Biogen Idec, Bayer Schering, Merck Serono, Teva Neuroscience, Baxter, Sanofi-Aventis Pharmaceuticals Inc., BioMS, Novartis, Bayer Pharmaceuticals Corp., RoFAR, Roche Diagnostics Corp., Genzyme Corp., and from the Danish Multiple Sclerosis Society.