REbif FLEXible Dosing in Early Multiple Sclerosis (MS)

Inclusion criteria

• Single, first clinical event suggestive of MS within 60 days prior to study Day 1, which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
• At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial
• EDSS 0 - 5.0 at least one time point during the screening period before start of treatment
• 18 and 50 years old, inclusive
• Willing to follow study procedures
• Written informed consent
• If female, subject must:

• be neither pregnant nor breast-feeding nor attempting to conceive
• use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is [i.e.] less than 1 percent [%] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner

Exclusion criteria

• Diagnosis of MS (per McDonald criteria 2005)
• Any other disease that could better explain the subject's signs and symptoms
• Complete transverse myelitis or bilateral optic neuritis
• Subject uses or has used any other approved MS disease-modifying drug (DMD)
• Any investigational drug or undergone an experimental procedure within 12 weeks prior to study Day 1
• Oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to study Day 1
• Total bilirubin greater than 2.5 times upper limit of normal (ULN)
• Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN
• Inadequate bone marrow reserve, defined as a total white blood cell count less than 3.0 x 109 per liter (/L), platelet count less than 75 x 109/L, hemoglobin less than 100 gram per liter (g/L)
• Current autoimmune disease
• Major medical or psychiatric illness (including history of or current severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
• History of seizures not adequately controlled by treatment
• Cardiac disease, such as angina, congestive heart failure or arrhythmia
• Known allergy to IFN-beta or the excipient(s) of the study medication
• Any condition that could interfere with the MRI evaluation;
• Known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
• Previously participated in this study
• Participated in any clinical trial within the past 6 months
• Any immunomodulatory or immunosuppressive therapy at any time prior to enrollment, including, but not limited to, the following products: any IFN, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e.g. natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous, immunoglobulins (Igs), cytokines or anti-cytokine therapy
• Any experimental MS treatment prior to trial entry, including, but not limited to, any statins (if given to prevent MS) and pentoxyfylline
• History of alcohol or drug abuse
• Intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
• Inability to administer subcutaneous injections either by self or by caregiver
• Moderate to severe renal impairment