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Inclusion Criteria:

* Patients diagnosed with active, relapsing MS course (defined by Lublin 2014 criteria). 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. Highly effective contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject, if accepted by the local regulation). NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal ARE NOT acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* For female subjects on the study, the vasectomized male partner should be the sole partner
* Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
* In case local regulations deviate from the contraception methods listed above, local regulations apply and will be described in the ICF.
* Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
* Subjects with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with an immunodeficiency syndrome.
* Subjects with a history of the following:

  1. History of any 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 the following laboratory abnormalities:

  1. Abnormal CD19+ B-cell levels at screening (defined as CD19 count \<110 cells per microliter)
  2. Leukopenia (defined as white blood cell (WBC) count \<4000 WBCs per microliter)
  3. Lymphopenia (defined as lymphocyte count \<1000 lymphocytes per microliter)
  4. Hypogammaglobulinemia defined as a level of \<500mg/dL will be excluded. All subjects with low serum immunoglobulins should be evaluated by a hematologic expert prior to exclusion in the study.
  5. Any abnormality of liver function tests, including ALT/SGPT, AST/SGOT, Alkaline phosphatase, total or direct bilirubin or GGT
* 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).
* Subjects with low affinity binders (LAB) for TSPO radioligand
* Subjects with abnormal serum creatinine levels (defined as \>1.3mg/dL) or Subjects with estimated glomerular filtration rate (eGFR) \<30ml/minute
* Patients with history of significant renal disease (dialysis, kidney transplant, single kidney, renal cancer, renal surgery)
* Patient presenting with cardiac disorders defined by at least one of the following conditions:
* Patient with recent cardiac history (within 6 months) of:

  * Acute coronary syndrome
  * Acute heart failure (class III or IV of the NYHA classification)
* History of significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
* Patient with history of cardiac failure class III or IV of the NYHA classification
* Patient with history of severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sinoatrial block)
* Syncope without known etiology within 3 months
* Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
* Subjects with any contraindications to PET/CT or MRI procedures (e.g. claustrophobia, MRI-incompatible implants or pacemakers, renal failure)
* Subjects with any significant or uncontrolled medical comorbidity
* Subjects with active hepatitis B
* Subjects at risk of hepatitis B reactivation (such as subjects with positive HBsAG or anti-Hepatitis B core antibodies) should be evaluated by a liver disease expert before inclusion, or should be excluded
* Subjects treated with other disease modifying treatments within their respective pre-specified washout periods will be excluded

• Boston, Massachusetts, United States