Assessment of Tecfidera® in Radiologically Isolated Syndrome (RIS)

NCT ID: NCT02739542

Last Updated: 2022-05-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-19

Study Completion Date

2021-03-31

Brief Summary

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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).

Detailed Description

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This is a multi-center, randomized, double-blinded study in which approximately 90 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.

Following informed consent and verification of entry criteria by the core units, study participants will be randomized 1:1 to either Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) or placebo. Clinical follow-up by the treating physician will occur at weeks 0, 48, 96, 144 and/or End of Study and during or immediately following clinical exacerbations. During clinical visits, comprehensive medical history data will be obtained by the treating physician. All reported acute or progressive clinical events will be adjudicated by the Central Clinical Unit. Clinical visits due to suspected exacerbations associated with CNS (central nervous system) demyelination, and associated diagnostic studies and treatments, will be covered under the medical standard of care by third party payers. A recommendation to re-evaluate the patient within 3 months following the clinical event to assess for extent of recovery will be made. In addition to the face-to-face visits described above, study participants will be contacted over the telephone at weeks 4, 8, 36, 60, 84, 108, and 132 to assess for medical or treatment difficulties and for study medication compliance. Standardized MRI studies of the brain will be performed at weeks 0, 96, 144 or End of Study. Clinical imaging studies of the brain and/or spinal cord performed during or immediately following the onset of a clinical exacerbation will be performed at the discretion of the site PI with scan costs covered under the medical standard of care. An end of study clinical MRI of the cervical spinal cord with and without contrast will be recommended to study participants at week 96 as medical standard of care.

Conditions

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Multiple Sclerosis (MS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tecfidera

Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily)

Group Type ACTIVE_COMPARATOR

Tecfidera

Intervention Type DRUG

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Placebo

Placebo by mouth twice daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Interventions

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Tecfidera

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Intervention Type DRUG

Placebo

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Intervention Type DRUG

Other Intervention Names

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Dimethyl fumarate

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Darin Okuda

PROFESSOR

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Darin T Okuda, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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Keck School of Medicine - USC - Department of Neurology

Los Angeles, California, United States

Site Status

Johns Hopkins University - Neurology

Baltimore, Maryland, United States

Site Status

Mayo Clinic Department of Neurology

Rochester, Minnesota, United States

Site Status

Washington University Department of Neurology

St Louis, Missouri, United States

Site Status

Cleveland Clinic - Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status

MS Clinical Care and Research Center, Dept of Neurology, Columbia University

New York, New York, United States

Site Status

Oklahoma Medical Research Foundation, MS Center of Excellence

Oklahoma City, Oklahoma, United States

Site Status

MS Treatment Center of Dallas

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16283615 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21387374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18202208 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19667020 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20610492 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21559385 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22740024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22076541 (View on PubMed)

Lebrun C, Le Page E, Kantarci O, Siva A, Pelletier D, Okuda DT; Club Francophone de Sclerose en Plaques (CFSEP); Radiologically Isolated Syndrome Consortium (RISC) Group. Impact of pregnancy on conversion to clinically isolated syndrome in a radiologically isolated syndrome cohort. Mult Scler. 2012 Sep;18(9):1297-302. doi: 10.1177/1352458511435931. Epub 2012 Feb 2.

Reference Type BACKGROUND
PMID: 22300971 (View on PubMed)

Okuda DT, Mowry EM, Cree BA, Crabtree EC, Goodin DS, Waubant E, Pelletier D. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology. 2011 Feb 22;76(8):686-92. doi: 10.1212/WNL.0b013e31820d8b1d. Epub 2011 Jan 26.

Reference Type BACKGROUND
PMID: 21270417 (View on PubMed)

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.

Reference Type RESULT
PMID: 19073949 (View on PubMed)

Okuda DT, Kantarci O, Lebrun-Frenay C, Sormani MP, Azevedo CJ, Bovis F, Hua LH, Amezcua L, Mowry EM, Hotermans C, Mendoza J, Walsh JS, von Hehn C, Vargas WS, Donlon S, Naismith RT, Okai A, Pardo G, Repovic P, Stuve O, Siva A, Pelletier D. Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome. Ann Neurol. 2023 Mar;93(3):604-614. doi: 10.1002/ana.26555. Epub 2022 Dec 10.

Reference Type DERIVED
PMID: 36401339 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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Other Identifiers

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102014-019

Identifier Type: -

Identifier Source: org_study_id

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