Evaluating safety, efficacy and pharmacokinetics of a modified regimen of ublituximab (ENHANCE)

Prior treatment

• 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 who have ever received ublituximab, alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab (including for non-MS indications)
• 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.)
• Previous serious opportunistic or atypical infection

Other illness

• Any severe or uncontrolled medical condition that could affect the participant’s ability to participate
• Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma
• 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)
• Evidence of chronic active or history of hepatitis B virus (HBV) 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 HCV Ab are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA

Other

• History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML)
• Females who are pregnant or nursing
• Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS)

• 18-65 years old
• Part C: Participants currently treated with an anti-CD20 agent for at least 6 months and meet the washout requirements listed in Appendix B – Washout Requirement for Prior Disease Modifying Therapies prior to W1D1. Note: Any exposure to therapies listed in Exclusion Criteria #14 remain exclusionary
• Part C: Discontinuation of current anti-CD20 must be due to suboptimal experience defined by having any of the following: a. One or more clinically reported relapse(s) b. One or more T1 Gd-enhanced lesion(s) c. Two or more new or enlarging T2 lesions on MRI d. Experiencing wearing-off effect e. B-cell repopulation between doses f. Persistent IRRs including on most recent anti-CD20 administration g. Inability to tolerate 2-hour infusion of ocrelizumab
• Part C: EDSS score ≤5.5 at screening
• Part C: Neurologically stable prior to first dose of ublituximab
• Part C: Acceptable laboratory parameters at screening
• Part C: Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for 6 months after the last dose of ublituximab
• Willing and able to comply with the study protocol in the investigator’s judgment
• Diagnosis of RMS (2017 Revised McDonald criteria)
• Participants must meet one of the following prior treatment definitions: a. Participants naïve to treatment. b. Participants previously treated with a DMT who have discontinued treatment prior to consent and meet the washout requirements listed in Appendix B – Washout Requirement for Prior Disease Modifying Therapies prior to W1D1. Note: Therapies listed in Exclusion Criteria #14 remain exclusionary.
• EDSS score ≤ 5.5 at screening
• Neurologically stable prior to first dose of ublituximab
• Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for protocol-specified time after the last dose of ublituximab
• Acceptable laboratory parameters at screening
• Part C: 18-65 years old
• Part C: Diagnosis of RMS (2017 Revised McDonald criteria)