Study Evaluating Rebif, Copaxone, and Tysabri for Active Multiple Sclerosis
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: BG00002 (natalizumab); interferon beta-1a; glatiramer acetate
Intervention description: 300 mg intravenous injection every 4 weeks; 44 mcg subcutaneous injection 3 times per week; 20 mg subcutaneous injection once daily
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Glatiramer Acetate; Natalizumab; (T,G)-A-L
Phase: Phase 3
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: MS

Summary:

      This was a multicenter, randomized, open-label, parallel-group, active-controlled study.
      Prior to randomization, participants were to have been treated with glatiramer acetate or
      interferon β-1a (44 μg). Participants were to be randomized to receive natalizumab,
      interferon β-1a 44 μg, or glatiramer acetate.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Have a diagnosis of relapsing remitting multiple sclerosis (MS) as defined by the
             revised McDonald Committee criteria (Polman 2005).

          2. Must have been treated with a stable regimen of either glatiramer acetate (20 mg per
             day subcutaneous) or interferon beta-1a (44 mcg 3 times per week subcutaneous) as
             their principal first therapy for MS for 6 to 18 months prior to randomization. (Note:
             prior treatment with another MS therapy of ≤ 30 days total duration is not
             exclusionary [e.g. titration to 44 mcg is allowed]).

          3. Have had disease activity within 12 months prior to screening while on therapy;
             disease activity must be observed after a minimum of 6 months on therapy. Qualifying
             disease activity is defined as:

               -  One or more clinical relapses OR

               -  Two or more new MRI lesions (gadolinium [Gd+] and/or T2 hyperintense) For
                  inclusion purposes: (a) a relapse is defined as neurologic signs and/or symptoms
                  documented in the medical record by a neurologist and of sufficient duration to
                  be determined by the Investigator or the Treating Physician as consistent with an
                  MS relapse or (b) MRI activity must be verified by the central reader center.

          4. Be naïve to natalizumab.

          5. Have a documented Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5,
             inclusive.

        Key Exclusion Criteria:

          1. Have a diagnosis of primary progressive, secondary progressive, or progressive
             relapsing MS (as defined by Lublin and Reingold, 1996). These conditions require the
             presence of continuous clinical disease worsening over a period of at least 3 months.
             Patients with these conditions may also have superimposed relapses, but are
             distinguished from relapsing-remitting patients by the lack of clinically stable
             periods or clinical improvement.

          2. Have known intolerance, contraindication to, or history of non-compliance with, the
             use of glatiramer acetate or interferon beta-1a.

          3. Have had an MS exacerbation (relapse) within 30 days prior to randomization AND/OR the
             patient has not stabilized from a previous relapse, in the opinion of the
             Investigator, prior to randomization.

          4. The patient is considered by the Investigator to be immunocompromised based on medical
             history, physical examination, laboratory testing, or due to prior immunosuppressive
             or immunomodulating treatment.

          5. Subjects for whom MRI is contraindicated, i.e., have pacemakers or other
             contraindicated implanted metal devices, have suffered or are at risk for side effects
             from gadolinium (Gd), or have claustrophobia that cannot be medically managed.

          6. History of any clinically significant (as determined by the Investigator) cardiac,
             endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary,
             neurologic, dermatologic, psychiatric, renal, or other major disease that would
             preclude participation in a clinical trial.

          7. History of malignant disease, including solid tumors and hematologic malignancies
             (with the exception of basal cell and squamous cell carcinomas of the skin that have
             been completely excised and are considered cured).

          8. Known history of human immunodeficiency virus (HIV).

          9. Positive test result for hepatitis C virus (test for hepatitis C virus antibody
             [HCVAb]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or
             hepatitis B core antibody [HBcAb]).

         10. History of transplantation or any anti-rejection therapy.

         11. History of progressive multifocal leukoencephalopathy (PML).

        NOTE: Other protocol-defined inclusion/exclusion criteria may apply.