Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Alemtuzumab
Intervention description: 10 mg/ml alemtuzumab intravenous infusion, sterile clear, colorless solution. dosage: 2 cycles. Month 0 dosed over 5 consecutive days: month 12 dosed over 3 consecutive days.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to
      protect the brain from inflammation and how it may enhance repair through remyelination.
    

Eligibility criteria:

        Inclusion Criteria

          1. Signed, informed consent form (ICF)

          2. Age 18 to 50 years old (inclusive) as of signing the ICF

          3. Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating
             white matter lesions attributable to MS within 10 years of screening

          4. Onset of MS symptoms (as determined by a neurologist) within 15 years of screening

          5. EDSS score 0.0 to 5.0 (inclusive)

          6. >=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

          7. Subjects previously enrolled and randomized to interferon beta 1a in the CARE-MS 323
             and 324 studies, and who will be treated with Alemtuzumab through the CARE-MS
             extension study will be eligible to participate in the immunology and MRI studies of
             this protocol.

        Exclusion Criteria

          1. Received prior therapy for MS other than corticosteroids within 28 days of screening;
             e.g., interferons, IV immunoglobulin, and glatiramer acetate

          2. Exposure to natalizumab within 6 months of screening

          3. Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine,
             cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other
             immunosuppressive agent other than systemic corticosteroid treatment

          4. Has any progressive form of MS

          5. History of malignancy (exception for basal cell skin carcinoma)

          6. Previous hypersensitivity reaction to other immunoglobulin product

          7. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis

          8. 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

          9. Seropositivity for human immunodeficiency virus (HIV)

         10. Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic
             lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel
             disease; severe psoriasis)

         11. Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies

         12. Active infection, e.g, deep-tissue infection, that the Investigator considers
             sufficiently serious to preclude study participation

         13. Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or
             active tuberculosis. Patients will be assessed for this risk based on a screening
             questionnaire.

         14. Infection with hepatitis B virus or hepatitis C virus

         15. Of childbearing potential with a positive serum pregnancy test

         16. Unwilling to agree to use a reliable and acceptable contraceptive method throughout
             the study period

         17. Major psychiatric disorder that is not adequately controlled by treatment

         18. Epileptic seizures that are not adequately controlled by treatment

         19. 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

         20. Medical, psychiatric, cognitive, or other conditions that, in the Investigator's
             opinion, 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

         21. Confirmed platelet count < the lower limit of normal (LLN) of the evaluating
             laboratory at Screening or documented at <100,000/uL within the past year on a sample
             without clumping

         22. Prior history of invasive fungal infections

         23. Cervical high risk human papillomavirus (HPV) positivity or abnormal cervical cytology
             other than abnormal squamous cells of undetermined significance (ASCUS). The patient
             may be eligible after the condition has been effectively treated (eg, follow-up HPV
             test is negative or cervical abnormality has been treated).

         24. Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II
             (HTLV-I/II) (testing required in endemic regions only)

         25. Any other illness or infection (latent or active) that, in the Investigator's opinion,
             could be exacerbated by alemtuzumab treatment

         26. Any hepatic or renal function value grade 2 or higher at Screening, with the exception
             of hyperbilirubinemia due to Gilbert's syndrome. See Table below, drawn from the
             National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0
             (CTCAE), published 09 August 2006