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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02342704
• Date of registration: 15/01/2015
• Prospective Registration: No
• Primary sponsor: Biogen
• Public title: Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants REVEAL
• 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
• Date of first enrolment: November 30, 2014
• Target sample size: 111
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02342704
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Australia, Czech Republic, Czechia, Denmark, France, Germany, Italy, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsing-Remitting Multiple Sclerosis

Intervention(s)

Drug: natalizumab

Drug: fingolimod

Primary Outcome(s)

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(s)

Proportion of Participants With No Evidence of Disease Activity (NEDA) [Time Frame: Up to Week 52]

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 T1-Gd+ Lesions [Time Frame: Baseline, Week 4, Week 12, Week 24]

Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24 [Time Frame: Baseline, Week 24]

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

Change From Baseline in SDMT at Week 52 [Time Frame: Baseline, Week 52]

Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24 [Time Frame: Baseline, Week 24]

Time to Complete Recovery From First Relapse [Time Frame: Up to Week 52]

Cumulative Risk of Relapse [Time Frame: Up to Week 52]

Time to First Relapse [Time Frame: Up to Week 52]

Secondary ID(s)

2013-004622-29

101MS408

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/06/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02342704