[S23.006] 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)
Amit Bar-Or,1Richard Grove,2Daren J. Austin,3Jerry Tolson,4Susan Vanmeter,5Eric Lewis,5Per Solberg Sorensen6
1Montreal, QC, Canada, 2Uxbridge, Middlesex, UBLondon, United Kingdom, 3Uxbridge, Middlesex,, United Kingdom, 4Raleigh, NC, USA, 5RTP, NC, USA, 6Copenhagen, Denmark
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 < 0.001]; corresponding analysis of Weeks 4-12 data estimated > 90% reductions for each dose ≥ 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
Category - MS and CNS Inflammatory Disease: Clinical Science
Tuesday, April 29, 2014 4:30 PM
S23: Platform Session: MS and CNS Inflammatory Disease: Novel Therapeutics (3:15 PM-5:00 PM)