Zenapax (Daclizumab) Admin to Pts With Multiple Sclerosis (ZAP MS): Effect of Intravenously Admin Humanized Monoclonal Antibody Against the Interleukin-2 Receptor Alpha Subunit (Daclizumab) on Inflammatory Activity in the Central Nervous System

Date de début de l'étude : 30 octobre 2003

* INCLUSION CRITERIA FOR PRE-TREATMENT SCREENING: To be eligible for entry into the study, patients must meet the following criteria at the time of enrollment. Re-assessment of the inclusion criteria will occur on day zero of the twelve-month treatment phase. Between the ages of 18 and 65 years, inclusive. Patients with relapsing-remitting MS according to published criteria. EDSS score between 1.0 and 5.5. Patients have either failed standard therapies (interferon-beta, glatiramer acetate) by clinical measures, or are not eligible for standard therapies, or opted not to start or continue with any of the standard therapies. Patients are able to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. Age criteria for inclusion in this study follow those of published diagnostic criteria for multiple sclerosis. Due to the uncommon occurrence of MS in individuals under the age of 18 and the requirement to study a large MS cohort to include these rarely occurring patients, this is an appropriate lower age range. Patient decision not to start, or not to continue with standard immunomodulatory therapy, has to be made by the patient after discussing conventional treatment options to ensure the patient has made an informed decision. Additionally, the consent document provided to the patient will explicitly state the currently approved therapies and their potential benefits. ELIGIBILITY CRITERIA FOR INITIATING THERAPY: To be eligible to proceed to the treatment phase of the study, patients must have at least two new gadolinium-enhancing lesions or greater in the four sequential baseline MRI scans (average of greater than or equal to 0.5 gadolinium-enhancing lesions or more). Patients can not have a relapse during 30 days before initiation of treatment. If a relapse occurs during this period and eligibility criteria are otherwise fulfilled, treatment (day one) will be delayed while corticosteroids are administered. If corticosteroids are administered, the MRI during that period will not be considered. An additional MRI will be added at 4 weeks following the completion of corticosteroids, to maintain a total of four MRI's that are analyzed in the baseline period. In the event of relapse, the baseline period will be prolonged, as necessary, to meet these criteria. EXCLUSION CRITERIA FOR PRE-TREATMENT SCREENING: Patients will be excluded from the study if any of the exclusion criteria exist at the time of enrollment. Re-assessment of the exclusion criteria will occur on day zero of the twelve month treatment phase. MEDICAL HISTORY: Diagnosis of secondary-progressive or primary-progressive MS, as defined by published diagnostic criteria. Abnormal screening/baseline blood tests exceeding any of the limits defined below: * Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values. * Total white blood cell count less than 3000/mm(3) * Platelet count less than 85000/mm(3) * Serum creatinine level greater than 2.0 mg/dl * Serological evidence of HIV or active hepatitis A, B or C infection since the effects of daclizumab are not defined in these patients * Positive pregnancy test Pregnant or breast-feeding female. History or signs of immunodeficiency. Concurrent clinically significant (as determined by the investigators) cardiac, immunological, pulmonary, neurological, renal or other major disease. Any contraindication to monoclonal antibody therapy. Contraindication to monoclonal antibody therapy includes prior history of serum-sickness or similar hypersensitivity reaction to receipt of monoclonal antibody or intravenous immunoglobulin therapies. Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not considered part of routine patient care. TREATMENT HISTORY: If prior treatments were administered, the patient must be off the following treatment agents for the required period prior to enrollment: * Glatiramer acetate, interferon-beta - 24 weeks * IVIg, azathioprine, methotrexate, cyclophosphamide, mitoxantrone, plasma exchange, cyclosporine, oral myelin, cladribine and other immunosuppressive treatments - 24 weeks * Corticosteroids - 6 weeks Prior treatment with other investigational drugs or procedures will be evaluated individually by the investigators. MISCELLANEOUS EXCLUSIONS: History of alcohol or drug abuse within the 5 years prior to enrollment. Female patients who are not post-menopausal or surgically sterile who are not using an acceptable method of contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Documentation that the patient is post-menopausal or surgically sterile must be available prior to enrollment. Male patients who are not surgically sterile and not practicing adequate contraception. Acceptability of various methods of contraception will be at the discretion of the investigator. Documentation that the patient is surgically sterile must be available prior to enrollment. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient returning for follow-up visits on schedule. Previous participation in this study.