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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02342704




Registration number
NCT02342704
Ethics application status
Date submitted
15/01/2015
Date registered
21/01/2015
Date last updated
9/06/2017

Titles & IDs
Public title
Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
Scientific 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
Secondary ID [1] 0 0
2013-004622-29
Secondary ID [2] 0 0
101MS408
Universal Trial Number (UTN)
Trial acronym
REVEAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing-Remitting Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - natalizumab
Treatment: Drugs - fingolimod

Experimental: natalizumab - Open-label natalizumab 300 mg IV every 4 weeks (Q4W)

Active Comparator: fingolimod - Open-label fingolimod 0.5 mg once daily orally


Treatment: Drugs: natalizumab
Administered as specified in the treatment arm

Treatment: Drugs: fingolimod
Administered as specified in the treatment arm

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cumulative Number of = 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions
Timepoint [1] 0 0
Up to Week 52
Secondary outcome [1] 0 0
Cumulative Number of New T1-Gd+ Lesions
Timepoint [1] 0 0
Baseline, Week 4, Week 12, Week 24
Secondary outcome [2] 0 0
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24 - As assessed by magnetic resonance imaging (MRI).
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52 - As assessed by MRI.
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Cumulative Number of New or Enlarging T2 Lesions
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to Week 52
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to Week 52
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Up to Week 52
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Up to Week 52
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline, Week 52

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - New Lambton Heights
Recruitment hospital [3] 0 0
Research Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Hradec Kralove
Country [12] 0 0
Czechia
State/province [12] 0 0
Jihlava
Country [13] 0 0
Czechia
State/province [13] 0 0
Ostrava - Poruba
Country [14] 0 0
Czechia
State/province [14] 0 0
Pardubice
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 5
Country [16] 0 0
Czechia
State/province [16] 0 0
Teplice
Country [17] 0 0
France
State/province [17] 0 0
Gard
Country [18] 0 0
France
State/province [18] 0 0
Gironde
Country [19] 0 0
France
State/province [19] 0 0
Haute Garonne
Country [20] 0 0
Germany
State/province [20] 0 0
Baden Wuerttemberg
Country [21] 0 0
Germany
State/province [21] 0 0
Hessen
Country [22] 0 0
Italy
State/province [22] 0 0
Roma
Country [23] 0 0
Spain
State/province [23] 0 0
Murcia
Country [24] 0 0
Spain
State/province [24] 0 0
Málaga
Country [25] 0 0
Spain
State/province [25] 0 0
Pontevedra
Country [26] 0 0
Spain
State/province [26] 0 0
Tenerife
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Girona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Sevilla
Country [31] 0 0
Sweden
State/province [31] 0 0
Göteborg
Country [32] 0 0
Sweden
State/province [32] 0 0
Stockholm
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Greater London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Strathclyde

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT02342704
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02342704