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Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants (REVEAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:
The primary objective of this study is to assess the effect of natalizumab compared to fingolimod on the evolution of new on-treatment T1-gadolinium-enhancing (Gd+) lesions to persistent black holes (PBH) over 52 weeks. The secondary objectives of this study in this study population are to assess the effect of natalizumab compared to fingolimod on: magnetic resonance imaging (MRI) measures of central nervous system (CNS) tissue destruction as measured by the number of new T1-Gd+ lesions; various other MRI measures of disease activity; No Evidence of Disease Activity (NEDA); Relapse on treatment over 52 weeks; The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).

Condition or disease Intervention/treatment Phase
Relapsing-Remitting Multiple Sclerosis Drug: natalizumab Drug: fingolimod Phase 4

Detailed Description:
This study also includes a Diffusion Tensor Imaging (DTI) sub-study that includes healthy volunteers. Healthy volunteers will not receive any study medication.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: natalizumab
Open-label natalizumab 300 mg IV every 4 weeks (Q4W)
Drug: natalizumab
Administered as specified in the treatment arm
Other Names:
  • BG00002
  • Tysabri

Active Comparator: fingolimod
Open-label fingolimod 0.5 mg once daily orally
Drug: fingolimod
Administered as specified in the treatment arm
Other Names:
  • FTY720
  • Gilenya




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Cumulative Number of New T1-Gd+ Lesions [ Time Frame: Baseline, Week 4, Week 12, Week 24 ]
  2. 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).

  3. 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.

  4. Cumulative Number of New or Enlarging T2 Lesions [ Time Frame: Baseline, Week 24 ]
  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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


Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Additional relevant MeSH terms:
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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