Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies
Condition: Relapsing Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: natalizumab
Intervention description: Administered as specified in the treatment arm
Intervention MeSH terms: Natalizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to determine the efficacy of natalizumab (Tysabri,
      BG00002) in participants with relapsing forms of multiple sclerosis (MS) who have failed
      Gilenya or BRACET (Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera) as measured by the
      proportion of participants with no evidence of disease activity (NEDA) at Year 1. The
      secondary objectives in this study population are: change in total T1 hypointense and total
      T2 hyperintense lesion volume; proportion of participants with NEDA at Year 2; evaluation of
      the impact of natalizumab on annualized relapse rate (ARR); and change in Multiple Sclerosis
      Impact Scale-29 (MSIS-29) physical impact score.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Subjects of childbearing potential must practice effective contraception from Day -1
             and be willing and able to continue contraception for duration of the study.

          -  Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011])
             at Screening.

          -  Must have been treated with Gilenya or Betaseron, Rebif, Avonex, Copaxone, Extavia,
             Tecfidera (BRACET) for at least the 12 months prior to Screening with no interruption
             of treatment greater than 1 month. Prior treatment with natalizumab is allowed;
             however, there must be a minimum 1 year since last natalizumab infusion and the
             Screening visit of this study, and if discontinuation of natalizumab in the past was
             not due to intolerance, anti-natalizumab antibodies, or efficacy loss.

          -  Must have had disease activity in the 6 months prior to Screening while on Gilenya or
             BRACET (as defined by at least 1 gadolinium enhancing lesion OR at least 2 new T2
             lesions compared with magnetic resonance imaging done within 12 months of screening OR
             clinical relapse, or Expanded Disability Status Scale [EDSS] progression of 1 point)

          -  Must have an EDSS score from 0 to 5.5 inclusive at Screening.

          -  Must have lymphocyte count that is documented as at or above the lower limit of normal
             (LLN) by the day before the first Tysabri infusion. If lymphocytes have not returned
             to LLN or above the day before the first Tysabri infusion (day 0), the subject has
             screen failed. The subject who screen fails is eligible to undergo Rescreening once;
             if additional Rescreening is considered, please contact the study medical monitor.

        Key Exclusion Criteria:

          -  History or positive test result at Screening for human immunodeficiency virus.

          -  History or positive test result at Screening for hepatitis C virus antibody or current
             hepatitis B infection (defined as positive for hepatitis B surface antigen and/or
             hepatitis core antibody).

          -  Prior treatment with natalizumab (either commercially or through a clinical study)
             within 1 year of Day -1.

          -  Contraindications to treatment with natalizumab as described in the Prescribing
             Information for each of the participating countries.

          -  Known allergy to natalizumab or any of its ingredients, or known to be
             anti-natalizumab antibody positive.

          -  Diagnosis of primary progressive MS, secondary progressive MS, and/or
             progressive-relapsing MS.

          -  An MS relapse that has occurred within the 30 days prior to Day -1 and/or the subject
             has not stabilized from a previous relapse prior to Day -1.

          -  Known active malignancies (subjects with cutaneous basal cell carcinoma that has been
             completely excised prior to study entry remain eligible).

          -  History of severe opportunistic infections (including progressive multifocal
             leukoencephalopathy) or any clinically significant cardiac, endocrinologic,
             hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic,
             dermatologic, psychiatric, and renal, or other major disease, as determined by the
             Investigator

          -  Clinically severe active infection within 1 month prior to Screening.

          -  Females breastfeeding, pregnant, or planning to become pregnant; women who are not
             post-menopausal or surgically sterile who are unwilling to practice contraception;
             women who have a positive pregnancy test result at Day -1.

          -  Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine,
             methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12
             months prior to Screening. Prior history of alemtuzumab use at any point in the past.

        NOTE: Other protocol-defined inclusion/exclusion criteria may apply