Inclusion Criteria:

• - Patients diagnosed with active, relapsing MS course.

Active disease is defined by at least 1 relapse during the previous 1 year or 2 relapses during the previous 2 years or a positive gadolinium-enhancing MRI scan or MRI scan with new or unequivocally enlarging T2 lesions in previous year.

• - Age 18 to 60 years.

• - EDSS 0 to 5.5.

• - Subjects either untreated or treated with disease modifying therapies other than those listed in exclusion criteria.

• - Agree to start treatment with ofatumumab and comply with study procedures for the duration of the study.

• - No other systemic disease or neurological disorders requiring chronic or acute steroid or other immunosuppressive treatment.

• - No known hypersensitivity reactions to contrast agents.

• - None of the exclusion criteria.

Exclusion Criteria:

• - Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator.

• - Subjects with primary progressive MS or SPMS without disease activity.

• - Disease duration of more than 10 years in patients with an EDSS score of 2 or less.

• - Subjects meeting criteria for neuromyelitis optica.

• - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

• - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 6 months after stopping study medication.

• - Subjects with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with an immunodeficiency syndrome.

• - Subjects with a history of the following: 1.

History of malignancy. 2. History of alcohol or drug abuse. 3. Primary or secondary immunodeficiency. 4. Prior hematopoietic stem cell transplantation. 5. History of transplantation or anti-rejection therapy.

• - Subjects with abnormal CD19, WBC, lymphocyte counts or abnormal IgG levels.

• - Subjects with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS).

• - Subjects with neurological symptoms consistent with PML or confirmed PML.

• - Subjects at risk of developing or having reactivation of syphilis or tuberculosis (eg subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated).

Testing for syphilis and tuberculosis will be done at Screening.

• - Subjects with low affinity binders (LAB) for TSPO radioligand.

• - Subjects with abnormal serum creatinine levels.

- Subjects with any contraindications to PET/CT or MRI procedures (e.g. claustrophobia, MRI-incompatible implants or pacemakers, renal failure) - Subjects treated with other disease modifying treatments within their respective pre-specified washout periods will be excluded:

Design: This is an open-label, observational, prospective, 9-month follow-up study to assess the efficacy of ofatumumab on microglia pathology in patients with MS, as measured by changes in microglial activation in the lesional and non-lesional, normal appearing white matter, cortical and subcortical grey matter, and peri-plaque area of chronic lesions in the brain. Initial Visit: During the first visit, subjects will be adminsitered the screening questionnaire (if that has not already been done over telephone). Subjects will review and eventually sign the consent form. They will be administered a physical examination, clinical assessment and standardized questionnaires for cognitive testing and/or other co-morbidities. In addition, blood samples will be drawn for genotype testing, infection screening, complete blood count and liver function test. Demographics, physical examinations and neurologic assessments will be conducted at Partners MS Center, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115. Genotype Testing: Blood sample drawn on the initial screening visit will be used to obtain genomic DNA for genotyping for polymorphism within the TSPO gene on chromosome 22q13.2, using a Taqman assay. High affinity and medium affinity binders will be included in the study, whereas low affinity binders will be excluded from the study. PET Scanning: For this study, all subjects will undergo five separate visits for [F-18]PBR06 PET scans, one visit before starting Ofatumumab treatment (day 0 baseline) and four more visits at approximately 5, 28, 90 and 273 days after initiating treatment. During the PET scan visits, all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection. The radiotracers will be produced using standardized procedures. At the time of imaging, the subjects will be positioned in the gantry of a high-resolution PET/CT camera. Head alignment will be made, relative to the canthomeatal line, using projected laser lines whose positions are known with respect to the slice positions of the scanner. A head support apparatus will be used to minimize head motion. Dynamic data over 120 minutes for PET quantification will be acquired, according to previously described methods for the tracer. MRI Scanning: All subjects will undergo five 3T brain MRIs with and without contrast, one before starting Ofatumumab treatment (day 0 baseline) and four more at 5, 28, 90 and 273 days after initiating treatment. MRI visits may precede or follow the PET scan visits within 2-3 days of each other. All women will be queried about their pregnancy status, use of contraception and last menstrual period. If a woman is of child bearing potential, she will undergo a urine pregnancy test. Subjects will undergo intravenous gadolinium contrast administration, during all visits. Hence, all women of child bearing potential will undergo urine pregnancy testing for this study. Clinical Follow-up Visits: Subjects will come in for five clinical visits, one visit before starting Ofatumumab treatment (day 0 baseline) and four more visits at 5, 28, 90 and 273 days after initiating treatment. However, if the patient meets all inclusion criteria at the screening visit, the screening and baseline visits may occur on the same day. During these visits, subjects will undergo a physical examination, clinical assessment and cognitive assessment using the measures outlined in section e of Study Procedures. A blood sample will be drawn to determine levels of sNfL, GFAP and other serum biomarkers. Visits will be conducted under the supervision of PI and other board-certified neurologists. Any adverse event reported by the patient or observed by the investigator will be recorded and reviewed at each clinical visit. Clinical Data: The following non-imaging, clinical data will be obtained: Expanded Disability Status Scale (EDSS), Timed 25-feet walk (T25W), 9-Hole Peg Test (9HPT), Four component MS Functional Composite (MSFC-4), Symbol-Digit Modality test (SDMT), cognitive and symptom questionnaires, vision testing, Levels of serum biomarkers. Clinical Safety Monitoring: Safety will be assessed at 0, 3, 6, and 9 months of the study including:

• - Pregnancy Testing: All women of childbearing potential will undergo a serum pregnancy test at the screening visit and at each of the following scheduled visits to the hospital.

The investigator will also review the contraception status of subjects at each visit.

• - Electrocardiogram (ECG): An ECG will be performed either at the screening visit or on day 0 clinical visit and at the end of the study.

• - Routine labs: Blood samples will be collected at the screening visit and at each visit time point.

Blood samples will be assessed for red blood cell count, hemoglobin, hematocrit, platelets, total white blood cell (WBC) count and WBC differential counts (neutrophils, lymphocytes, basophils, eosinophils, monocytes) as well as for electrolytes (Na, K, Cl, bicarbonate, Ca, Mg, P), random glucose, total protein, blood urea nitrogen, albumin, alkaline phosphatase, ALT, AST, GGT, total bilirubin, conjugated bilirubin, creatinine, amylase, , C-Reactive protein.

• - Samples for total IgM and IgG levels at baseline, 3, 6 and 9 months.

• - Patient diary review.

• - Monthly telephone interview.

Drug Administration/Dosing: At the end of the baseline clinic visit, subjects will be instructed by one of the investigators on proper drug administration technique. The first injection of ofatumumab will be performed under the guidance of an appropriately trained healthcare professional in the clinical space at the Partners MS Center.

Arms

Experimental: Subjects diagnosed with relapsing forms of multiple sclerosis

We plan to enroll 10 subjects with relapsing MS. All enrolled subjects will receive Ofatumumab 20 mg every 4 weeks, subcutaneously for 9 months during the study. Loading doses will be administered initially at 1, 7 and 14 days. During the study period, all enrolled subjects will undergo five PET scans using [F-18] PBR06 at 0, 5, 28, 90 and 273 days after starting treatment with Ofatumumab.

Interventions

Drug: - Ofatumumab

Ofatumumab (OMB157) is a fully human anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly subcutaneous injection that is in development for MS. Ofatumumab drug product (also referred as OMB157) is formulated as 20 mg/0.4 mL (50 mg/mL) solution for injection, provided in autoinjectors, for subcutaneous administration. The autoinjectors contain a small overfill to allow for a complete withdrawal of the labeled amount (20 mg) of ofatumumab.

Drug: - [F-18]PBR06

PET radiopharmaceutical. Subjects will undergo [F-18]PBR06-PET (microglial activation).