immune globulin intravenous (igiv) to treat relapsing, remitting multiple sclerosis

Conditions: Multiple Sclerosis, Relapsing-Remitting

Summary: the trial will study 2 doses of immune globulin intravenous (human), 10% caprylate/chromatography purified (igiv-c) for the number of relapses that occur in a 1 year treatment period.

this trial is designed as a multi-national, randomized, double-blind, placebo-controlled prospective trial with three parallel groups. one hundred twenty (120) patients, 40 per treatment arm, with relapsing-remitting (rr) multiple sclerosis will be enrolled in this trial. eligible patients must have a diagnosis of ms as per the mcdonald criteria. in addition, patients must have a diagnosis of relapsing-remitting course of ms defined as periods of worsening of neurological function with full recovery or with sequelae and residual deficit upon recovery; periods between disease relapses characterized by lack of disease progression. patients must also have active disease with at least 1 defined documented relapse in the last year. during a 2 month run-in period, 2 mris will be performed 6 weeks apart and patients will be stratified based on the presence or absence of 1 or more gadolinium enhancing lesions on the first mri (gd-enhancing lesion yes-no) and will be randomized to one of two dose regimens of igiv-c or matching placebo. patients will receive study drug infusions every 4 weeks for 48 weeks for a total of 12 infusions. patients will be evaluated by mri every 6 weeks and by clinical assessments every 3 months. a follow-up visit will occur 4 weeks after the last infusion. the treatment groups are as follows: * igiv-c - 0.2 g/kg body weight (bw)/infusion (2 ml/kg bw) * igiv-c - 0.4 g/kg bw/infusion (4 ml/kg bw) * placebo (0.1% albumin) - 4 ml/kg bw/infusion for blinding purposes, at each infusion, all patients will receive a total volume of 4 ml/kg bw. for patients receiving 0.2 g/kg bw of igiv-c, the final volume of 4 ml/kg bw will be adjusted by the addition of dextrose 5%. placebo will be supplied as albumin 5% or albumin 25% and diluted with either dextrose 5% or saline to a final concentration of 0.1% albumin. dose adaptation will be performed for subsequent infusions in case the patient's body weight has changed \> 10%. the maximum amount available per infusion will be 400 ml (8 vials) calculated for a patient with a body weight of 100 kg. the suggested initial infusion rate will be 0.02 ml/kg/min for the first 15 minutes. if there is no evidence of a hypersensitivity reaction, the infusion may be given at a slowly increasing rate over the next 30 minutes up to a maximum allowable rate of 0.08 ml/kg/min. as such, the infusion for a 70 kg patient will take approximately 1hour 15 min. the overall infusion time may have a range from 1 to 2 hours.

Eligibility criteria:
inclusion criteria: * symptoms consistent with multiple sclerosis up to 5 years * diagnosis of multiple sclerosis according to mcdonald criteria. * diagnosis of relapsing-remitting (rr) multiple sclerosis (ms) (defined as periods of worsening of neurological function with full recovery or with sequelae and residual deficit upon recovery; periods between disease relapses characterized by lack of disease progression * kurtzke extended disability status scale (edss) \< 5.0 * at least 1 defined and documented relapse during the last year. prior relapses where symptoms were due solely to a change in bowel/bladder function or cognitive function will not be considered relapses as defined by this protocol and therefore not counted for inclusion into the study. * females or males; females of childbearing potential must use adequate contraception * clinically stable for at least 30 days prior to entry * at least 9 hyperintense t2 lesions on mri or 1 gd-enhancing lesion according to mcdonald/barkhof dissemination-in-space criteria at entry * patients who have been informed about available treatments and decided, not to go on these treatments * written informed consent obtained prior to the initiation of any study related procedures exclusion criteria: * females who are pregnant, breast feeding, or if, of childbearing potential, unwilling to practice adequate contraception throughout the study * prior therapy with azathioprine or any immunosuppressant agents within 6 months prior to study entry * prior steroid, methylprednisolone or adrenocorticotropic hormone (acth) therapy within 30 days prior to study entry * therapy with interferons (betaseron®, avonex®, rebif®), glatiramer acetate (copaxone®) or igiv within 3 months prior to study entry or during the study * use of an investigational compound within 6 months prior to study entry * previous lymphoid irradiation or prior to treatment with cyclophosphamide, methotrexate or mitoxantrone * cardiac insufficiency (nyha iii/iv), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease (ccs iii or iv), or malignant hypertension * history of renal insufficiency or serum creatinine levels greater than 2.5 mg/dl (221 µmol/l) * known selective immunoglobulin a (iga) deficiency or known antibodies to iga * conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin g (igg) utilization (e.g., protein-losing enteropathies, nephrotic syndrome) * any medical, psychiatric or other circumstances which impede or restrict the patient's participation in the study or any contraindication to contrast enhanced mri (e.g.,pacemaker, aortic clip or any metal implant) * patients with clinically significant medical conditions including, but not limited to cardiac, pulmonary, hepatic, hematological (e.g. known coagulation disorder, history of deep venous thrombosis and/or pulmonary embolism), endocrine,or renal dysfunction, autoimmune disorders, severe environmental allergies or chronic infections