Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants (REVEAL)
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ClinicalTrials.gov Identifier: NCT02342704 |
Recruitment Status :
Terminated
(Business Decision)
First Posted : January 21, 2015
Results First Posted : June 9, 2017
Last Update Posted : June 9, 2017
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Condition or disease | Intervention/treatment | Phase |
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Relapsing-Remitting Multiple Sclerosis | Drug: natalizumab Drug: fingolimod | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 111 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Multicenter, Randomized, Open-Label Study to Assess the Impact of Natalizumab Versus Fingolimod on Central Nervous System Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis Subjects |
Actual Study Start Date : | November 30, 2014 |
Actual Primary Completion Date : | May 18, 2016 |
Actual Study Completion Date : | May 18, 2016 |

Arm | Intervention/treatment |
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Experimental: natalizumab
Open-label natalizumab 300 mg IV every 4 weeks (Q4W)
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Drug: natalizumab
Administered as specified in the treatment arm
Other Names:
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Active Comparator: fingolimod
Open-label fingolimod 0.5 mg once daily orally
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Drug: fingolimod
Administered as specified in the treatment arm
Other Names:
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- Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions [ Time Frame: Up to Week 52 ]
- Cumulative Number of New T1-Gd+ Lesions [ Time Frame: Baseline, Week 4, Week 12, Week 24 ]
- Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24 [ Time Frame: Baseline, Week 24 ]As assessed by magnetic resonance imaging (MRI).
- Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52 [ Time Frame: Baseline, Week 52 ]As assessed by MRI.
- Cumulative Number of New or Enlarging T2 Lesions [ Time Frame: Baseline, Week 24 ]
- Proportion of Participants With No Evidence of Disease Activity (NEDA) [ Time Frame: Up to Week 52 ]NEDA was defined as all of the following: no relapses; no 12-week confirmed disability progression based on Expanded Disability Status Scale (EDSS; defined as an increase of 1.0 or more on the EDSS from baseline of 1.0 or more, or an increase of 1.5 or more from a baseline score of 0) that was sustained for 12 weeks; no new T1-Gd+ lesions on brain MRI. No new or enlarging T2-hyperintense lesions.
- Time to First Relapse [ Time Frame: Up to Week 52 ]A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.
- Cumulative Risk of Relapse [ Time Frame: Up to Week 52 ]A clinical relapse was defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.
- Time to Complete Recovery From First Relapse [ Time Frame: Up to Week 52 ]12-week confirmed complete EDSS recovery from first on-treatment relapse is defined as an EDSS score that is equal to or lower than the last pre-relapse EDSS score and sustained for at least 12 weeks.
- Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24 [ Time Frame: Baseline, Week 24 ]The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.
- Change From Baseline in SDMT at Week 52 [ Time Frame: Baseline, Week 52 ]The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0-110 in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution.

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Key Inclusion Criteria for MS Patients:
- Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria) at study screening with EDSS score from 0.0 to 5.5.
- If the subject is on Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA) at study screening:
- He/she must have been on therapy for at least 6 months (unless experiencing highly active disease), have at least 9 T2-hyperintense lesions on a brain MRI scan, and have experienced ≥1 relapse within the last 6 months prior to study screening with ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening
- If the subject has highly active disease, regardless of whether they are disease-modifying therapy (DMT)-naïve or had previous exposure to Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA), they must have had ≥2 disabling relapses in the 12 months prior to study screening and either ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening
Key Exclusion Criteria for MS Patients:
- Diagnosis of Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis.
- History or positive test result at study screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
- Prior treatment with natalizumab or fingolimod.
- History of or known active malignant disease, including solid tumors and hematologic malignancies (subjects with cutaneous basal and squamous cell carcinoma that has been completely excised and considered cured prior to study screening remain eligible).
- History of opportunistic infections or any clinically significant major disease, as determined by the Investigator.
- A clinically significant infectious illness (e.g., pneumonia, septicemia) within the 1 month prior to study screening.
- History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.
- Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab), or exposure to intravenous immunoglobulin (IGIV), monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins in the last 12 months prior to study screening.
- History of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 months.
- Treatment with Class Ia (e.g., procainamide, quinidine, ajmaline, disopyramide) or Class III (amiodarone, bretylium, dofelitide, sotalol, ibulitide, azilimide) anti-arrhythmic drugs.
- Concurrent therapy with drugs that slow heart rate (e.g., beta-blockers, heart-rate lowering calcium channel blockers such as diltiazem or verapamil, or digoxin).
- Hypertension not controlled with prescribed medications.
- History of severe respiratory disease, pulmonary fibrosis or class III or IV chronic obstructive pulmonary disease.
- The use of live or live attenuated vaccination within 8 weeks of study screening.
Key Inclusion Criteria for Healthy Volunteers:
- Subjects who are generally healthy as demonstrated by physical examination and by medical history, with no history or evidence of major illnesses, diseases, or disorders.
- Subjects of childbearing potential must practice effective contraception and be willing and able to continue contraception for duration of the study.
- No history of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.
Key Exclusion Criteria for Healthy Volunteers:
- Claustrophobia sufficient to interfere with generating reliable MRI scans.
- History of other major illness including neurological disorders as determined by the Investigator.
- Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects), which would be a contraindication for MRI.
- Women who are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02342704
United States, Colorado | |
Research Site | |
Aurora, Colorado, United States, 80045 | |
Research Site | |
Colorado Springs, Colorado, United States, 80907 | |
United States, Florida | |
Research Site | |
Port Charlotte, Florida, United States, 33952 | |
United States, Georgia | |
Research Site | |
Atlanta, Georgia, United States, 30327 | |
United States, Iowa | |
Research Site | |
Des Moines, Iowa, United States, 50314 | |
United States, Pennsylvania | |
Research Site | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Tennessee | |
Research Site | |
Knoxville, Tennessee, United States, 37922 | |
United States, Texas | |
Research Site | |
Round Rock, Texas, United States, 78681 | |
Research Site | |
San Antonio, Texas, United States, 78229 | |
United States, Washington | |
Research Site | |
Seattle, Washington, United States, 98122 | |
Research Site | |
Tacoma, Washington, United States, 98405 | |
United States, Wisconsin | |
Research Site | |
Milwaukee, Wisconsin, United States, 53215 | |
Australia, New South Wales | |
Research Site | |
Camperdown, New South Wales, Australia, 2050 | |
Research Site | |
New Lambton Heights, New South Wales, Australia, 2305 | |
Australia, Victoria | |
Research Site | |
Heidelberg, Victoria, Australia, 3084 | |
Czechia | |
Research Site | |
Brno, Czechia, 625 00 | |
Research Site | |
Brno, Czechia, 656 91 | |
Research Site | |
Hradec Kralove, Czechia, 500 05 | |
Research Site | |
Jihlava, Czechia, 58633 | |
Research Site | |
Ostrava - Poruba, Czechia, 708 52 | |
Research Site | |
Pardubice, Czechia, 532 03 | |
Research Site | |
Praha 5, Czechia, 150 06 | |
Research Site | |
Teplice, Czechia, 415 01 | |
France | |
Research Site | |
Nimes, Gard, France, 30029 | |
Research Site | |
Libourne Cedex, Gironde, France, 33505 | |
Research Site | |
Toulouse cedex 9, Haute Garonne, France, 31059 | |
Germany | |
Research Site | |
Freiburg, Baden Wuerttemberg, Germany, 79106 | |
Research Site | |
Erbach, Hessen, Germany, 64711 | |
Italy | |
Research Site | |
Gianicolense, Roma, Italy, 87-00151 | |
Research Site | |
Roma, Italy, 00189 | |
Spain | |
Research Site | |
El Palmar, Murcia, Spain, 30120 | |
Research Site | |
Malaga, Málaga, Spain, 29010 | |
Research Site | |
Vigo, Pontevedra, Spain, 36204 | |
Research Site | |
Santa Cruz de Tenerife, Tenerife, Spain, 38010 | |
Research Site | |
Barcelona, Spain, 08035 | |
Research Site | |
Girona, Spain, 17007 | |
Research Site | |
Madrid, Spain, 28006 | |
Research Site | |
Sevilla, Spain, E 41009 | |
Sweden | |
Research Site | |
Göteborg, Sweden, 41345 | |
Research Site | |
Stockholm, Sweden, 17176 | |
United Kingdom | |
Research Site | |
London, Greater London, United Kingdom, SE5 9NU | |
Research Site | |
Glasgow, Strathclyde, United Kingdom, G51 4TF |
Study Director: | Medical Director | Biogen |
Responsible Party: | Biogen |
ClinicalTrials.gov Identifier: | NCT02342704 |
Other Study ID Numbers: |
101MS408 2013-004622-29 ( EudraCT Number ) |
First Posted: | January 21, 2015 Key Record Dates |
Results First Posted: | June 9, 2017 |
Last Update Posted: | June 9, 2017 |
Last Verified: | May 2017 |
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases |
Autoimmune Diseases Immune System Diseases Natalizumab Fingolimod Hydrochloride Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents |