A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis

Treatment tested

• Alemtuzumab

  CAMPATH-1 antigen inhibitor

• Campath®
• Interferon beta-1a

  Interferon alpha/beta receptor agonist

Compared with

• Interferon beta-1a

  Interferon alpha/beta receptor agonist

Other measures (4)

Inclusion Criteria: * Signed informed consent form (ICF) * Male or non-pregnant, non-lactating female participants, 18 to 50 years of age (inclusive) as of signing the ICF * Diagnosis of MS per McDonald's update of the Poser criteria, including cranial MRI consistent with those criteria (McDonald, 2001, Ann Neurol) * Onset of first MS symptoms within 3 years prior to Screening as of signing the ICF * Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at the screening and Baseline visits * At least 2 completed clinical episodes of MS in the 2 years prior to study entry (that is, the initial event if within 2 years of study entry plus at least 1 relapse, or at least 2 relapses if the initial event was between 2 and 3 years prior to study entry) * In addition to the clinical criteria, at least 1 enhancing lesion on any 1 of up to 4 screening gadolinium-enhanced MRI brain scans during a maximum 3-month run-in period (inclusive of the Month 0 Baseline scan) Exclusion Criteria: * Previous immunotherapy for MS other than steroids, including treatment with interferons, intravenous immunoglobulin (IVIG), glatiramer acetate, and mitoxantrone * Personal history of thyroid autoimmune disease * Personal history of clinically significant autoimmune disease (for example, inflammatory bowel disease, diabetes, lupus, severe asthma) * History of thyroid carcinoma (previous thyroid adenoma was acceptable and was not considered an exclusion criterion) * History of malignancy (except for basal cell skin carcinoma if disease-free for at least 5 years) * Any disability acquired from trauma or another illness that, in the opinion of the Investigator, interfered with evaluation of disability due to MS * Previous treatment with alemtuzumab * History of anaphylaxis following exposure to humanized monoclonal antibodies * Inability to undergo MRI with gadolinium administration * Female participants of childbearing potential with a positive serum pregnancy test at screening or Baseline * Male and female participants who did not agree to use effective contraceptive method(s) during the study * Impaired renal function (that is, serum creatinine greater than or equal to 2 times the upper limit of normal [ULN]) * Untreated, major depressive disorder * Epileptic seizures that were not adequately controlled by treatment * Suicidal ideation * Major systemic disease or other illness that, in the opinion of the Investigator, have compromised participant safety or interfered with the interpretation of study results * Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-thyroid stimulating hormone (TSH) receptor antibodies; known seropositivity for human immunodeficiency (HIV) * Intolerance of pulsed corticosteroids, especially a history of steroid psychosis * Presence of a monoclonal paraprotein * Participants who had any form of MS other than relapsing-remitting * Participants currently participating in a clinical study of an experimental or unapproved/unlicensed therapy

This was a Phase II, randomized, open-label, rater-blinded, three-arm study comparing two different doses of alemtuzumab (Lemtrada™) and one dose of subcutaneous (SC) interferon beta-1a (Rebif®) in participants with early, active relapsing-remitting multiple sclerosis (MS) who had not been previously treated with MS therapies other than steroids. The study was conducted for an initial period of 3 years and a follow-up to 5 years or more.