Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
Condition: Relapsing-Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: natalizumab; fingolimod
Intervention description: Administered as specified in the treatment arm; Administered as specified in the treatment arm
Intervention MeSH terms: Natalizumab; Fingolimod Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 111.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

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).
    

Eligibility 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