9-month Study to Assess the Efficacy of Ofatumumab on Microglia in Patients With Relapsing Forms of Multiple Sclerosis

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 1.3mg/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 ant