Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Alemtuzumab 12 mg; Alemtuzumab 24 mg; Interferon beta-1a
Intervention description: Alemtuzumab 12 milligram (mg) per day intravenous (IV) infusion on 5 consecutive days at Month 0, followed by alemtuzumab 12 mg per day IV infusion on 3 consecutive days at Month 12.; Alemtuzumab 24 mg per day IV infusion on 5 consecutive days at Month 0, followed by alemtuzumab 24 mg per day IV infusion on 3 consecutive days at Month 12.; Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Alemtuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 840.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis

Summary:

      The purpose of this study was to establish the efficacy and safety of two different doses of
      alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in
      comparison with subcutaneous interferon beta-1a (Rebif®). The study enrolled participants who
      had received an adequate trial of disease-modifying therapies but experienced at least 1
      relapse during prior treatment, and who met a minimum severity of disease as measured by
      magnetic resonance imaging (MRI). Participants had monthly laboratory tests and comprehensive
      testing every 3 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent form (ICF)

          -  Age 18 to 55 years (inclusive) as of the date the ICF was signed

          -  Diagnosis of MS per update of McDonald criteria

          -  Onset of MS symptoms (as determined by a neurologist; could be retrospectively) within
             10 years of the date the ICF was signed

          -  Expanded Disability Status Scale (EDSS) score 0.0 to 5.0 (inclusive) at Screening

          -  Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the
             24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior
             to the date the ICF was signed, with objective neurological signs confirmed by a
             physician, nurse practitioner, or other Genzyme-approved health-care provider and the
             objective signs could be identified retrospectively

          -  >=1 MS relapse during treatment with a beta interferon therapy or glatiramer acetate
             after having been on that therapy for >=6 months within 10 years of the date the ICF
             was signed

          -  MRI scan demonstrating white matter lesions attributable to MS and meeting at least 1
             of the following criteria, as determined by the neurologist or a radiologist: >=9 time
             constant 2 (T2) lesions at least 3 millimeter (mm) in any axis; a gadolinium- (Gd-)
             enhancing lesion at least 3 mm in any axis plus >=1 brain T2 lesions; and a spinal
             cord lesion consistent with MS plus >=1 brain T2 lesion

        Exclusion Criteria:

          -  Received prior therapy with alemtuzumab

          -  Current participation in another clinical study or previous participation in CAMMS323
             (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, CARE-MS I)

          -  Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6
             months. Participants who received one of these medications more than 6 months before
             the date the ICF was signed were eligible for study entry if approval was granted by
             Genzyme

          -  Any progressive form of MS

          -  History of malignancy (except basal skin cell carcinoma)

          -  CD4 +, CD8 +, CD19 + (that is, absolute CD3 + CD4 + , CD3 + CD8 + , or CD19 + /mm 3 )
             count, absolute neutrophil count less than (<) lower limit of normal (LLN) at
             screening; if abnormal cell count(s) returned to within normal limits (WNL),
             eligibility could be reassessed

          -  Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency,
             hemophilia, Von Willebrand's disease, disseminated intravascular coagulation,
             fibrinogen deficiency, or clotting factor deficiency)

          -  Significant autoimmune disease including but not limited to immune cytopenias,
             rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders,
             vasculitis, inflammatory bowel disease, severe psoriasis

          -  Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that
             is, above the LLN)

          -  Active infection or at high risk for infection