Assessment of Tecfidera® in Radiologically Isolated Syndrome (RIS) (ARISE)

April 13, 2022 updated by: Darin Okuda, University of Texas Southwestern Medical Center

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90089
        • Keck School of Medicine - USC - Department of Neurology
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University - Neurology
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Department of Neurology
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Department of Neurology
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Cleveland Clinic - Lou Ruvo Center for Brain Health
    • New York
      • New York, New York, United States, 10032
        • MS Clinical Care and Research Center, Dept of Neurology, Columbia University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Medical Research Foundation, MS Center of Excellence
    • Texas
      • Dallas, Texas, United States, 75246
        • MS Treatment Center of Dallas
      • Dallas, Texas, United States, 75390-8806
        • UT Southwestern Medical Center
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center
      • Tacoma, Washington, United States, 98405
        • MultiCare Institute for Research and Innovation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tecfidera
Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily)
Drug: 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.
Other Names:
  • Dimethyl fumarate
Placebo Comparator: Placebo
Placebo by mouth twice daily.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)
Time Frame: 96 weeks
The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination from randomization into the trial.
96 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Lesion Volume on T2-weighted MRI
Time Frame: Baseline, 96 weeks
Change in lesion volume on T2-weighted MRI is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
Baseline, 96 weeks
Number of Newly Enlarging T2 Lesions
Time Frame: 96 weeks
Number of newly enlarging T2 lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
96 weeks
Number of New T2 Lesions
Time Frame: 96 weeks
Number of new T2 lesions as measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
96 weeks
Newly Enlarging T2 Lesions and New T2 Lesions Combined
Time Frame: 96 weeks
Newly enlarging T2 lesions and new T2 lesions combined is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
96 weeks
Number of Contrast Enhancing Lesions
Time Frame: 96 weeks
Number of contrast enhancing lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
96 weeks
Change in the Number of Participants With Brain Atrophy
Time Frame: Baseline, 96 weeks
Change in the number of participants with brain atrophy is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.
Baseline, 96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

Biogen

Investigators

  • Principal Investigator: Darin T Okuda, MD, UT Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2016

Primary Completion (Actual)

March 31, 2021

Study Completion (Actual)

March 31, 2021

Study Registration Dates

First Submitted

March 16, 2016

First Submitted That Met QC Criteria

April 14, 2016

First Posted (Estimate)

April 15, 2016

Study Record Updates

Last Update Posted (Actual)

May 11, 2022

Last Update Submitted That Met QC Criteria

April 13, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 102014-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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