SHS_543107 REPP CUTS 16017

Multi-center, Randomized, Double-blinded Assessment of Tecfidera® in Extending the Time to a First Attack in Radiologically Isolated Syndrome (RIS) (ARISE)

The purpose of this investigation is to systematically study the efficacy of Tecfidera in those individuals who possess incidental white matter anomalies within the brain following a MRI study that is performed for a reason other than for the evaluation of MS (multiple sclerosis). This is a multi-center, randomized, double-blinded study in which approximately 210 RIS (radiologically isolated syndrome) subjects will be treated with either Tecfidera or placebo for 2 years (1:1 randomization). Study participants, along with the treating and examining physicians, will be blinded to treatment assignment. Central Clinical and Imaging Units will screen all potential study subjects for inclusion/exclusion criteria. We expect to enroll all RIS subjects within the U.S.

Inclusion criteria

•Males and females meeting 2009 RIS criteria
•Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated > 2009
•Incidental anomalies identified on MRI of the brain or spinal cord with the primary reason for the acquired MRI resulting from an evaluation of a process other than MS
•CNS white matter anomalies meeting the following MRI criteria: Ovoid, well-circumscribed, and homogeneous foci with or without involvement of the corpus callosum; T2-hyperintensities measuring > 3mm2 and fulfilling 3 of 4 Barkhof-Tintoré criteria for dissemination in space; CNS anomalies not consistent with a vascular pattern; qualitative determination that CNS anomalies have a characteristic appearance of demyelinating lesions
•MRI anomalies do not account for clinically apparent neurological impairments in patients

Exclusion criteria

•Women who are pregnant or nursing
•Incomplete medical history or radiological data
•History of remitting clinical symptoms consistent with multiple sclerosis lasting > 24 hours prior to CNS imaging revealing anomalies suggestive of MS
•History of paroxysmal symptoms associated with MS (i.e. Lhermitte's or Uhthoff's phenomena)
•CNS MRI anomalies are better accounted for by another disease process
•The subject is unwilling or unable to comply with the requirements of the study protocol
•Exposure to a disease modifying therapy for MS/RIS within the past 3 months
•Exposure to high-dose glucocorticosteroid treatment within the past 30 days
•Participation in other clinical trials involving treatment with a disease-modifying agent
Phase IV
Multiple Sclerosis
Pavle Repovic, M.D.
University of Texas Southwestern Medical Center
Caryl Tongco
  • Swedish Medical Center