A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
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.
The aims of MS therapy are to prevent the progression of disease and accumulation of
 long-term disability. The hypothesis underlying this study was that aggressive treatment of
 inflammation in the brain early in the course of MS would protect the participant from
 disease progression and accumulating disability.

 This protocol compared two different doses of alemtuzumab and high-dose, high frequency of SC
 interferon beta-1a to evaluate the safety profiles of the respective treatments and to
 evaluate efficacy in terms of:

 -  Slowing the sustained accumulation of disability in participant with MS;

 -  Reducing the frequency of relapses experienced by participant with MS; and

 -  Reducing the harmful effects of MS on the brain, as assessed by magnetic resonance
 imaging (MRI)

 Participants who received alemtuzumab during the initial 36-month treatment period may have
 been eligible for re-treatment with alemtuzumab in the extension study CAMMS03409
 (NCT00930553) to evaluate:

 -  How long the effects of prior alemtuzumab treatment lasted;

 -  If additional treatments with alemtuzumab continued to reduce the effects of MS; and

 -  What kind of side effects participants experienced upon retreatment with alemtuzumab
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