Study to Evaluate the Maintenance of Efficacy When Transitioning From Anti-CD20 Therapy to Ublituximab (ENHANCE)

Inclusion Criteria: Diagnosis of RMS (2017 Revised McDonald criteria) within prior 10 years. Participants currently treated with ocrelizumab must have received 2 fully infused initial 300 mg ocrelizumab IV infusions and at least 1 fully infused 600 mg ocrelizumab IV infusion 6 months later (+/- one month). The last ocrelizumab dose must have occurred 5-9 months prior to baseline (i.e., first dose/Week 1 Day 1 [W1D1]). Participants currently being treated with rituximab must have received at least 2 full infusions of rituximab 500 mg - 1000 mg IV every 6 months (+/- one month) or initial loading regimens of rituximab (i.e., 500 mg - 1000 mg on Day 1 and on Day 15), and at least 1 fully infused rituximab dose (i.e., 500 mg - 1000 mg) 6 months later (+/- one month). The last full rituximab dose must have occurred within 5-9 months prior to baseline (i.e., first dose/W1D1). Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening. Neurologically stable for > 30 days prior to first dose of ublituximab. Exclusion Criteria: Suboptimal response to anti-CD20 therapy in the prior 6 months defined as Documented MRI worsening (≥ 2 active T1-weighted Gd-enhancing lesions, any new or enlarging T2 lesions assessed from a standard of care MRI) and/or Clinical worsening as measured by EDSS or any clinical measure documented. Documented relapse within the 12 months prior to W1D1. History of severe or life-threatening IRR on prior anti-CD20 therapy. Primary-progressive multiple sclerosis (PPMS) or inactive Secondary Progressive MS (SPMS). Active chronic (or stable but treated with immune therapy) disease of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency, etc.). Current evidence or known history of clinically significant infection, including: chronic, recurrent, or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to chronic urinary tract infection, chronic pulmonary infection with bronchiectasis, tuberculosis, or active hepatitis C virus (HCV). Previous serious opportunistic or atypical infection. Evidence of chronic active or history of hepatitis B virus (HBV) infection as evidenced by a detectable hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody (HBcAb), or chronic hepatitis C infection. Participants with positive hepatitis C virus antibody (HCV Ab) are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML). Receipt of any live or live-attenuated vaccines (including vaccines for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration. Participants requiring frequent and chronic use of high-dose corticosteroids. Participants requiring treatment with intravenous immune globulin (IVIG) for decreased immunoglobulins within the 12 months prior to W1D1. Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma. Participants who have ever received alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab.