Advanced MRI Measures of Repair in Alemtuzumab Treated Patients

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). There are many forms of MS; although the majority are Relapsing Remitting (RRMS) representing approximately 80% of the cases. The disease appears to be more inflammatory in RRMS as manifested by an increase in Gadolinium (Gd) enhancement on MRI and an increase in inflammatory bio-assay markers.

Alemtuzumab; a humanized monoclonal antibody that targets the CD52 molecule present on T and B lymphocytes, natural killer (NK) cells, and monocytes and macrophages; effects rapid and sustained lymphocyte depletion and is approved for the treatment of B-cell chronic lymphocytic leukemia in many countries under the names CAMPATH or MabCAMPATH.

There are two parts to this Investigator Sponsored Trial (IST):

• To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
• To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.

Inclusion criteria

• Signed, informed consent form
• Age 18 to 50 years old (inclusive)
• Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening
• Onset of MS symptoms within 15 years of screening
• Neurostatus (EDSS) score 0.0 to 5.0 (inclusive)
• 2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with 1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician.

Exclusion criteria

• Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferon's, IV immunoglobulin, and glatiramer acetate
• Exposure to natalizumab within 6 months of screening
• Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment
• Has any progressive form of MS
• History of malignancy (exception for basal cell skin carcinoma)
• Previous hypersensitivity reaction to other immunoglobulin product
• Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
• CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count <LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed
• Seropositivity for human immunodeficiency virus (HIV)
• Significant autoimmune disease (e.g, 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
• Active infection
• Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis.
• Infection with hepatitis B virus or hepatitis C virus
• Of childbearing potential with a positive serum pregnancy test
• Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period
• Major psychiatric disorder that is not adequately controlled by treatment
• Epileptic seizures that are not adequately controlled by treatment
• Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results
• Medical, psychiatric, cognitive, or other conditions
• Confirmed platelet count the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at 100,000/L within the past year on a sample without clumping
• Prior history of invasive fungal infections
• Cervical high risk human papilloma virus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS).
• Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only)
• Any other illness or infection (latent or active) that, in the Investigator's opinion, could be exacerbated by alemtuzumab treatment
• Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert's syndrome.