Assessment of Tecfidera® in Radiologically Isolated Syndrome (RIS)
Multi-center, Randomized, Double-blinded Assessment of Tecfidera® in Extending the Time to a First Attack in Radiologically Isolated Syndrome (RIS) (ARISE)
What it found
Results are posted in the registry, but without a statistical test of the main measure. See the numbers below.
What was tested
Treatment tested
- Dimethyl fumarate
Kelch-like ECH-associated protein 1 inhibitor
Placebo
- Placebo
Results by group
The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)
96 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Tecfidera | 89.69 weeks | 23.99 (Standard Deviation) | 44 |
| Placebo | 77.81 weeks | 32.19 (Standard Deviation) | 43 |
Tecfidera
Placebo
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Tecfidera | 44 | 4 (9.1%) | 0 |
| Placebo | 43 | 4 (9.3%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)
96 weeks
Other measures (6)
Change in Lesion Volume on T2-weighted MRI
Baseline, 96 weeks
MRI lesionsNumber of Newly Enlarging T2 Lesions
96 weeks
MRI lesionsNumber of New T2 Lesions
96 weeks
MRI lesionsNewly Enlarging T2 Lesions and New T2 Lesions Combined
96 weeks
MRI lesionsNumber of Contrast Enhancing Lesions
96 weeks
MRI lesionsChange in the Number of Participants With Brain Atrophy
Baseline, 96 weeks
MRI lesionsBrain volume loss
Who could take part
Early (CIS/RIS) · 18 and over
Show the full criteria
Inclusion criteria
1. Males and females meeting 2009 RIS criteria 2. Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated > 2009 3. 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 4. 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 5. MRI anomalies do not account for clinically apparent neurological impairments in patients
Exclusion criteria
1. Women who are pregnant or nursing 2. Incomplete medical history or radiological data 3. History of remitting clinical symptoms consistent with multiple sclerosis lasting > 24 hours prior to CNS imaging revealing anomalies suggestive of MS 4. History of paroxysmal symptoms associated with MS (i.e. Lhermitte's or Uhthoff's phenomena) 5. CNS MRI anomalies are better accounted for by another disease process 6. The subject is unwilling or unable to comply with the requirements of the study protocol 7. Exposure to a disease modifying therapy for MS/RIS within the past 3 months 8. Exposure to high-dose glucocorticosteroid treatment within the past 30 days 9. Participation in other clinical trials involving treatment with a disease-modifying agent
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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).
Papers
Results
Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome.Ann Neurol · 2023
Results
Okuda DT, Mowry EM, Beheshtian A, Waubant E, Baranzini SE, Goodin DS, Hauser SL, Pelletier D. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology. 2009 Mar 3;72(9):800-5. doi: 10.1212/01.wnl.0000335764.14513.1a. Epub 2008 Dec 10.Background
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703.Background
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.Background
Lebrun C, Bensa C, Debouverie M, De Seze J, Wiertlievski S, Brochet B, Clavelou P, Brassat D, Labauge P, Roullet E; CFSEP. Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):195-8. doi: 10.1136/jnnp.2006.108274.Background
Siva A, Saip S, Altintas A, Jacob A, Keegan BM, Kantarci OH. Multiple sclerosis risk in radiologically uncovered asymptomatic possible inflammatory-demyelinating disease. Mult Scler. 2009 Aug;15(8):918-27. doi: 10.1177/1352458509106214.Background
Lebrun C, Blanc F, Brassat D, Zephir H, de Seze J; CFSEP. Cognitive function in radiologically isolated syndrome. Mult Scler. 2010 Aug;16(8):919-25. doi: 10.1177/1352458510375707. Epub 2010 Jul 7.Background
De Stefano N, Stromillo ML, Rossi F, Battaglini M, Giorgio A, Portaccio E, Hakiki B, Malentacchi G, Gasperini C, Santangelo M, Bartolozzi ML, Sormani MP, Federico A, Amato MP. Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis. PLoS One. 2011 Apr 29;6(4):e19452. doi: 10.1371/journal.pone.0019452.Background
Gabelic T, Radmilovic M, Posavec V, Skvorc A, Boskovic M, Adamec I, Milivojevic I, Barun B, Habek M. Differences in oligoclonal bands and visual evoked potentials in patients with radiologically and clinically isolated syndrome. Acta Neurol Belg. 2013 Mar;113(1):13-7. doi: 10.1007/s13760-012-0106-1. Epub 2012 Jun 28.Background
Giorgio A, Stromillo ML, Rossi F, Battaglini M, Hakiki B, Portaccio E, Federico A, Amato MP, De Stefano N. Cortical lesions in radiologically isolated syndrome. Neurology. 2011 Nov 22;77(21):1896-9. doi: 10.1212/WNL.0b013e318238ee9b. Epub 2011 Nov 9.
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History
Started
Mar 2016
Main results due
Mar 2021
Finished
Mar 2021
Results posted
May 2022