Immune Globulin Intravenous (IGIV) To Treat Relapsing, Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Study to Compare the Effects of Different Dose Regimens of IGIV Chromatography (IGIV-C), 10% Treatment on Relapses in Patients With Relapsing Remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified
* Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>IGIV-C 0.2 g/kg bw/infusion (2 ml/kg bw) | Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified<br> <br> * Other names: NDC 13533-645-71;|
| Experimental: Group 2<br>IGIV-C 0.4 g/kg bw/infusion (4 ml/kg bw) | Drug: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified<br> <br> * Other names: NDC 13533-645-71;|
| Placebo Comparator: Group 3<br>placebo (0.1% albumin) 4 ml/kg bw/infusion | Drug: Albumin (Human) 25%, United States Pharmacopeia (USP)<br> <br> * Other names: NDC 13533-692-71;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Relapse Free Subjects (no Relapse) | A relapse was defined for the purposes of this study as the appearance or reappearance of one or more neurological symptoms or worsening of an old symptom attributed to multiple sclerosis (MS) persisting for at least 48 hours and immediately preceded by a relatively stable or improving neurological state of at least 30 days. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI) |  | 1 year |