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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 37
- 主要终点
- Percentage of Relapse Free Subjects (no Relapse)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Group 1
IGIV-C 0.2 g/kg bw/infusion (2 ml/kg bw)
干预措施: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified (Drug)
Group 2
IGIV-C 0.4 g/kg bw/infusion (4 ml/kg bw)
干预措施: Immune Globulin IV [Human], 10% Caprylate/Chromatography Purified (Drug)
Group 3
placebo (0.1% albumin) 4 ml/kg bw/infusion
干预措施: Albumin (Human) 25%, United States Pharmacopeia (USP) (Drug)
结局指标
主要结局
Percentage of Relapse Free Subjects (no Relapse)
时间窗: 12 months
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.
次要结局
- Effect on the Combined Unique Lesion Activity on Magnetic Resonance Imaging (MRI)(1 year)