PMID- 32351164 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20210924 IS - 1477-0970 (Electronic) IS - 1352-4585 (Print) IS - 1352-4585 (Linking) VI - 27 IP - 3 DP - 2021 Mar TI - A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis. PG - 420-429 LID - 10.1177/1352458520918375 [doi] AB - BACKGROUND: Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. OBJECTIVE: The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. METHODS: This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. RESULTS: In all cohorts (N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p = 0.003) and a 10.6% decrease in T2 lesion volume (p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). CONCLUSION: Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses. FAU - Fox, Edward AU - Fox E AD - Central Texas Neurology Consultants, Round Rock, TX, USA. FAU - Lovett-Racke, Amy E AU - Lovett-Racke AE AD - Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA. FAU - Gormley, Matthew AU - Gormley M AD - Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA. FAU - Liu, Yue AU - Liu Y AD - Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA. FAU - Petracca, Maria AU - Petracca M AD - Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Cocozza, Sirio AU - Cocozza S AD - Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA/Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy. FAU - Shubin, Richard AU - Shubin R AD - SC3 Research Group, Inc., Pasadena, CA, USA. FAU - Wray, Sibyl AU - Wray S AD - Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA. FAU - Weiss, Michael S AU - Weiss MS AD - TG Therapeutics, Inc., New York, NY, USA. FAU - Bosco, Jenna A AU - Bosco JA AD - TG Therapeutics, Inc., New York, NY, USA. FAU - Power, Sean A AU - Power SA AD - TG Therapeutics, Inc., New York, NY, USA. FAU - Mok, Koby AU - Mok K AD - TG Therapeutics, Inc., New York, NY, USA. FAU - Inglese, Matilde AU - Inglese M AD - Medical Center, Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200430 PL - England TA - Mult Scler JT - Multiple sclerosis (Houndmills, Basingstoke, England) JID - 9509185 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD20) RN - U59UGK3IPC (ublituximab) SB - IM MH - Antibodies, Monoclonal MH - Antigens, CD20 MH - Humans MH - Magnetic Resonance Imaging MH - *Multiple Sclerosis MH - *Multiple Sclerosis, Relapsing-Remitting/drug therapy MH - Recurrence PMC - PMC7897779 OTO - NOTNLM OT - TG-1101 OT - Ublituximab OT - gadolinium-enhancing lesions OT - magnetic resonance imaging OT - multiple sclerosis OT - relapse COIS- Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.F. received personal fees from Biogen, Chugai, EMD Serono, Genentech/Roche, Celgene, MedDay, Novartis, Sanofi Genzyme, and TG Therapeutics, outside the submitted work. A.E.L.-R. received grants from TG Therapeutics, during the conduct of the study, and personal fees from Novartis, outside the submitted work. M.G., Y.L., and R.S. have nothing to disclose. M.P. received personal fees from TG Therapeutics, Inc., outside the submitted work. S.C. received personal fees from Shire and Genzyme, outside the submitted work. S.W. received personal fees from Alkermes, Bayer, Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis, Sanofi, and TG Theraputics, outside the submitted work. M.S.W., J.A.B., S.A.P., and K.M. have employment and stock ownership with TG Therapeutics. M.I. received grants from TG Therapeutics, during the conduct of the study; Teva Neuroscience, National Institutes of Health (NIH), and National Multiple Sclerosis Society (NMSS), outside the submitted work. EDAT- 2020/05/01 06:00 MHDA- 2021/09/25 06:00 PMCR- 2021/02/22 CRDT- 2020/05/01 06:00 PHST- 2020/05/01 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] PHST- 2020/05/01 06:00 [entrez] PHST- 2021/02/22 00:00 [pmc-release] AID - 10.1177_1352458520918375 [pii] AID - 10.1177/1352458520918375 [doi] PST - ppublish SO - Mult Scler. 2021 Mar;27(3):420-429. doi: 10.1177/1352458520918375. Epub 2020 Apr 30.