Relapsing-Remitting Multiple SclerosisPhase 4REVEALNCT02342704
Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
A Phase 4 study testing natalizumab and fingolimod in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 42 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis
- What is being tested?
- natalizumab and fingolimod
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 42 sitesin 9 countries
- Study dates
- 30 Nov 2014to 18 May 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- 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
Trial locations and contacts
42 sites in 9 countries.
42 sites in 9 countries
United States12 sites
Research Site
Atlanta, Georgia, 30327
Research Site
Aurora, Colorado, 80045
Research Site
Colorado Springs, Colorado, 80907
Research Site
Des Moines, Iowa, 50314
Research Site
Knoxville, Tennessee, 37922
Research Site
Milwaukee, Wisconsin, 53215
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Port Charlotte, Florida, 33952
Research Site
Round Rock, Texas, 78681
Research Site
San Antonio, Texas, 78229
Research Site
Seattle, Washington, 98122
Research Site
Tacoma, Washington, 98405
Czechia8 sites
Research Site
Brno, 625 00
Research Site
Brno, 656 91
Research Site
Hradec Králové, 500 05
Research Site
Jihlava, 58633
Research Site
Ostrava - Poruba, 708 52
Research Site
Pardubice, 532 03
Research Site
Prague, 150 06
Research Site
Teplice, 415 01
Spain8 sites
Research Site
Barcelona, 08035
Research Site
El Palmar, Murcia, 30120
Research Site
Girona, 17007
Research Site
Madrid, 28006
Research Site
Málaga, Málaga, 29010
Research Site
Santa Cruz de Tenerife, Tenerife, 38010
Research Site
Seville, E 41009
Research Site
Vigo, Pontevedra, 36204
Australia3 sites
Research Site
Camperdown, New South Wales, 2050
Research Site
Heidelberg, Victoria, 3084
Research Site
New Lambton Heights, New South Wales, 2305
France3 sites
Research Site
Libourne, Gironde, 33505
Research Site
Nîmes, Gard, 30029
Research Site
Toulouse, Haute Garonne, 31059
Germany2 sites
Research Site
Erbach im Odenwald, Hesse, 64711
Research Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Italy2 sites
Research Site
Gianicolense, Roma, 87-00151
Research Site
Roma, 00189
United Kingdom2 sites
Research Site
Glasgow, Strathclyde, G51 4TF
Research Site
London, Greater London, SE5 9NU
About this study
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
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).
Read the 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.
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Being tested
- natalizumab, fingolimod
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natalizumabDrug
Also called BG00002, Tysabri
Administered as specified in the treatment arm
fingolimodDrug
Also called FTY720, Gilenya
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| natalizumab | Experimental | Open-label natalizumab 300 mg IV every 4 weeks (Q4W) Receives: Drug: natalizumab |
| fingolimod | Active comparator | Open-label fingolimod 0.5 mg once daily orally Receives: Drug: fingolimod |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions
Measured: Up to Week 52
Secondary outcomes (10)
Cumulative Number of New T1-Gd+ Lesions
Measured: Baseline, Week 4, Week 12, Week 24
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
As assessed by magnetic resonance imaging (MRI).
Measured: Baseline, Week 24
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
As assessed by MRI.
Measured: Baseline, Week 52
Cumulative Number of New or Enlarging T2 Lesions
Measured: Baseline, Week 24
Proportion of Participants With No Evidence of Disease Activity (NEDA)
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.
Measured: Up to Week 52
Time to First Relapse
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.
Measured: Up to Week 52
Cumulative Risk of Relapse
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.
Measured: Up to Week 52
Time to Complete Recovery From First Relapse
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.
Measured: Up to Week 52
Change From Baseline in Symbol Digit Modalities Test (SDMT) at 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.
Measured: Baseline, Week 24
Change From Baseline in SDMT at 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.
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2015 (estimated)
- Study start30 Nov 2014
- Primary completion18 May 2016
- Study completion18 May 2016
Why it stopped: Business Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsing-Remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02342704
- Sponsor's protocol ID
- 101MS408
- Other IDs
- 2013-004622-29
- Acronym
- REVEAL
- Status last verified
- May 2017
- First submitted
- 15 Jan 2015
- Last updated
- 9 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Butzkueven H, Licata S, Jeffery D, Arnold DL, Filippi M, Geurts JJ, Santra S, Campbell N, Ho PR; REVEAL Investigators. Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study. BMJ Open. 2020 Oct 20;10(10):e038861. doi: 10.1136/bmjopen-2020-038861.
PubMed 33082194
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02342704
- Acronym / sponsor ID
- REVEAL / 101MS408
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision
- Enrolment
- 111 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2014 (actual)
- Primary completion
- 18 May 2016 (actual)
- Study completion
- 18 May 2016 (actual)
- First posted
- 21 Jan 2015 (estimated)
- Results
- Posted 9 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| natalizumab | Experimental | Drug: natalizumabOpen-label natalizumab 300 mg IV every 4 weeks (Q4W) |
| fingolimod | Active comparator | Drug: fingolimodOpen-label fingolimod 0.5 mg once daily orally |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| natalizumabAlso: BG00002, TysabriAdministered as specified in the treatment arm | Drug | natalizumab |
| fingolimodAlso: FTY720, GilenyaAdministered as specified in the treatment arm | Drug | fingolimod |
Primary outcome
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
10 secondary outcomes
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
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
Time frame: Baseline, Week 52
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
Time to First Relapse
Time frame: Up to Week 52
Cumulative Risk of Relapse
Time frame: Up to Week 52
Time to Complete Recovery From First Relapse
Time frame: Up to Week 52
Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
Time frame: Baseline, Week 24
Change From Baseline in SDMT at Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33082194Butzkueven H, Licata S, Jeffery D, Arnold DL, Filippi M, Geurts JJ, Santra S, Campbell N, Ho PR; REVEAL Investigators. Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study. BMJ Open. 2020 Oct 20;10(10):e038861. doi: 10.1136/bmjopen-2020-038861.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
42 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing natalizumab and fingolimod in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 42 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Czechia, Spain, Australia, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02342704, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2017.