Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study One (CARE-MS I)

• Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ]
• Relapse Rate [ Time Frame: 2 years ]

• Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Change from baseline in Expanded Disability Status Scale (EDSS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Percent change from baseline in magnetic resonance imaging (MRI)-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ]
• Change from baseline in EDSS [ Time Frame: 2 years ]
• Acquisition of disability as measured by change from baseline in MSFC [ Time Frame: 2 years ]
• Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ]

The purpose of this study is to establish the efficacy and safety of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enroll patients who have not previously received treatment to suppress MS, except steroids. Patients will have monthly laboratory tests and comprehensive testing every 3 months.

Every patient will receive active treatment; there is no placebo. Patients who qualify will be randomly assigned to treatment with either alemtuzumab or Rebif® at a 2:1 ratio (ie, 2 given alemtuzumab for every 1 given Rebif®). Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif® will be self-injected 3 times per week for 2 years. All patients will be required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests will be performed at least monthly. Participation in this study will end 2 years after the start of treatment for each patient. Additionally, patients who receive alemtuzumab may be followed in CAMMS03409 (NCT 00930553) an extension study for safety and efficacy assessments. Patients who receive Rebif® and complete 2 years on study may be eligible to receive alemtuzumab on the extension study.

• Biological: alemtuzumab
  12 mg per day administered through IV, once a day for 5 consecutive days at Month 0 and 12 mg per day administered through IV, once a day for 3 consecutive days at Month 12.
• Biological: interferon beta-1a (Rebif®)
  44 mcg administered 3-times weekly by SC injections for 2 years

• Experimental: alemtuzumab 12 mg
  Intervention: Biological: alemtuzumab
• Active Comparator: interferon beta-1a (Rebif ®) 44mcg
  Intervention: Biological: interferon beta-1a (Rebif®)

• Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. Epub 2005 Jul 27.
• CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. Interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801.
• Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.

Inclusion Criteria:

• Diagnosis of MS and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years
• Onset of MS symptoms within 5 years
• EDSS score 0.0 to 3.0
• ≥2 MS attacks within 24 months, with ≥1 attack within 12 months

Exclusion Criteria:

• Received prior therapy for MS other than corticosteroids
• Exposure to immunosuppressive or immunomodulatory agents other than systemic corticosteroid treatment
• Received treatment with a monoclonal antibody for any reason
• Previous treatment with any investigational drug (i.e. medication that is not approved at any dose for any indication)
• Has any progressive form of MS
• Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS
• Major systemic disease that cannot be treated or adequately controlled by therapy
• Active infection or high risk for infection
• Autoimmune disorder (other than MS)
• Impaired hepatic or renal function
• History of malignancy, except basal skin cell carcinoma
• Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
• Known bleeding disorder
• Of childbearing potential with a positive serum pregnancy test, pregnant or lactating
• Current participation in another clinical study
• Previous hypersensitivity reaction to any immunoglobulin product
• Known allergy or intolerance to interferon beta, human albumin, or mannitol
• Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
• Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver
• Inability to undergo MRI with gadolinium administration
• Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)