Effects of Ublituximab on Motor Functions in Multiple Sclerosis

Prior treatment

• History of life-threatening infusion reaction on ublituximab, any of its ingredients, or prior anti-clusters of differentiation 20 (CD20) therapy.
• Receipt of a live vaccine within 6 weeks before baseline.
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
• Infection requiring hospitalization or treatment with i.v. antibiotics within four weeks prior to baseline visit or oral antibiotics within two weeks prior to baseline visit.
• History of alcohol or drug abuse within 24 weeks prior to baseline.
• Receipt of any live of live-attenuated vaccines within 4 weeks prior to first drug product administration.
• Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer).
• Systemic corticosteroid therapy within 4 weeks prior to screening.
• Any previous treatment with alemtuzumab (Campath), anti-cluster of differentiation 4 (CD4), cladribine, mitoxantrone, daclizumab, tecfidera (BG12), teriflunomide, laquinimod, total body irradiation or bone marrow transplantation.
• Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil (MMF), cyclosporine, methotrexate, or natalizumab within 24 months prior to screening.
• Treatment with intravenous immunoglobulin within 12 weeks prior to baseline.
• Treatment with anti-CD20 or other B cell-directed treatment.
  • Exclusions Related to Motor Function
• Have received neurological treatment, such as Botox, in the past six months.
• Surgery on back, hip, shoulder, or total joint replacement of hip or knee joint less than two years ago.

Other illness

• History of MS types other than relapsing MS at screening (such as primary-progressive MS, inactive SPMS).
• Have any other known neurological diseases which may mimic MS, including but not limited to: Neuromyelitis optica, Lyme disease, untreated vitamin B12 deficiency, neurosarcoidosis, and cerebrovascular disorders.
• History of clinically significant central nervous system (CNS) trauma (e.g., traumatic brain injury, cerebral contusion, spinal cord compression, etc.).
• History of liver disease.
• Active hepatitis B virus (HBV) confirmed by positive results for Hepatitis B surface antigen (HBsAg) and anti-HBV tests.
• Current evidence or known history of clinically significant infection.
• Suffering from coexisting psychiatric disorders, neurological disorders, or severe medical illness.
• Significant cognitive impairment (Montreal Cognitive Assessment or Montreal Cognitive Assessment (MoCA) score \< 24).
• Skin is allergic to transparent double-side tapes.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Significant or uncontrolled somatic disease or any other significant disease that may preclude a patient from participating in the study.
• Congestive heart failure (NYHA III or IV functional severity).
• Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds.
• History or known presence of recurrent or chronic infection (e.g., hepatitis B or C, HIV, syphilis, tuberculosis).
• History of progressive multifocal leukoencephalopathy (PML).
• History of malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that has been previously completely excised with documented clear margins.
• Weak or blind vision may impair their ability to walk.
  • Exclusions Related to Musculoskeletal, Cardiovascular, and Orthopedic Conditions
• Heart attack, angioplasty, or coronary artery bypass graft in the past six months.
• Congestive heart failure (NYHA III or IV functional severity).
• Respiratory conditions (lung cancer, bronchitis, emphysema, asthma, shortness of breath) not under regular medical care or the patient is medically unstable.

Lab values

• History or laboratory evidence of coagulation disorders.
  • Exclusions Related to Medications

Other

• Basic Exclusion Criteria
• Hypersensitive to any of the ingredients of ublituximab.
• Do not understand English.
  • Exclusions Related to General Health
• Pregnancy or lactation.
• Current severe depression and/or suicidal ideation.
• New onset, unstable orthopedic comorbid diagnoses (within 3 months and uncontrolled).
• History or currently active primary or secondary immunodeficiency.
• History or currently active primary or secondary immunodeficiency.
• Lack of peripheral venous access.
• Cannot walk at least 25 feet and stand for at least 30 seconds independently.
• Broken bones as an adult in the past year.

• Ability to provide written, informed consent and to be compliant with the schedule of protocol assessments.
• Ages between 18 and 55 years old at screening.
• Clinically confirmed active, relapsing forms of MS based on the revised McDonald criteria.
• Can walk at least 25 feet independently with or without assistive devices at screening.
• Can stand independently for at least 30 seconds.
• Not pregnant at screening and throughout the study.
  • A negative urine or serum pregnancy test must be available for premenopausal women and for women \< 12 months after the onset of menopause at screening, unless they have undergone surgical sterilization.
  • Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of \< 1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment.
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of the ovaries and/or uterus).
  • Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tube ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception.
  • Examples of barrier methods supplemented with the use of spermicide include male or female condom, vaginal ring, cap, diaphragm, or sponge.
• No other neurological conditions and recent musculoskeletal injuries.
• Can read and understand English.
• No significant cognitive impairment.