Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of IGIV-Chromatography (IGIV-C), 10% Treatment in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 32
- 主要终点
- Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
研究概览
简要总结
The intent of this study is to demonstrate the efficacy and safety of Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in newly or previously diagnosed CIDP subjects. Eight courses of treatment with either placebo or IGIV-C will occur every 3 weeks. Neurological function will be measured by Inflammatory Neuropathy Cause and Treatment (INCAT) scores. Patients who deteriorate or show no improvement between day 16 and month 6 will receive the alternate study drug for an additional 6 months.
详细描述
110 subjects, 55 per treatment group, with newly or previously diagnosed CIDP defined by INCAT neurophysiological diagnostic criteria will be enrolled into the trial. Patients will not be replaced if they discontinue prematurely.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of CIDP must be made by a neurologist specializing/experienced in neuromuscular diseases based on: a) Progressive or relapsing motor and sensory dysfunction of more than one limb resulting from neuropathy over the 2 months prior to the date informed consent is obtained, and b) Cerebrospinal fluid (CSF) less than 50 white cells/µl since CIDP diagnosis (CSF testing studies are NOT mandatory)
- •Fulfillment of INCAT neurophysiological criteria for focal demyelinating polyradiculoneuropathy
- •Overall INCAT score between 2-9 and significant disability in upper or lower limb function in at least 2 limbs. (An INCAT score of 2 must be exclusively from leg disability to qualify.)
排除标准
- •Treatment with IGIV or plasma within 3 months prior to entry
- •Steroids (Prednisolone or equivalent) > 10 mg/day or equivalent (i.e., > 20 mg every 2 days) during the last 3 months prior to entry
- •Treatment with immunomodulatory/immunosuppressive agents (azathioprin, tacrolimus,cyclosporin, Muromonab-CD3 (OKT3), any interferon), previous lymphoid irradiation or prior treatment with cyclophosphamide, methotrexate, mitoxantrone or any other immunosuppressant drug within the past 6 months prior to entry
- •Concomitant use of supplements containing any amount of fish oil within 30 days prior to entry
- •Respiratory impairment requiring mechanical ventilation
- •Myelopathy or evidence of central demyelination or persisting neurological deficits from stroke, central nervous system (CNS) trauma or peripheral neuropathies of other cause which include diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), uremic, toxic and familial neuropathies
- •Pure motor syndrome fulfilling criteria for multifocal motor neuropathy with conduction block. Lower motor neuron disorder with motor weakness in an upper limb, without sensory deficit and with proximal conduction block (50% decrease in amplitude/area with proximal distal stimulation ) in motor nerves and normal sensory nerve conduction studies.
- •Clinical or known evidence of associated systemic diseases that might cause neuropathy, including but not limited to connective tissue disease, HIV infection, hepatitis, Lyme disease, cancer (with the exception of benign skin cancer), Castleman's disease and systemic lupus erythematosus, diabetes mellitus (defined as a history of type 1 or type 2 diabetes with fasting plasma glucose ≥ 7.0 mmol/L), a malignant plasma cell dysplasia, immunoglobulin M (IgM) paraproteinemia, and amiodarone therapy.
- •History of anaphylaxis or severe systemic response to immunoglobulin or with a blood product.
- •Cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic pressure >120 mmHg or systolic >170 mmHg).
- •Females who are pregnant, breast feeding, or if of childbearing potential, unwilling to practice adequate contraception throughout the study.
- •Known hyperviscosity.
- •History of renal insufficiency or serum creatinine levels > 221 µmol/L (2.5 mg/dL).
- •Known selective immunoglobulin A (IgA) deficiency.
- •Other investigational drugs received within the 30 days prior to entry
- •Conditions whose symptoms and effects could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome).
- •Known hypercoagulable state.
- •Mentally challenged adult subjects who cannot give independent informed consent.
- •Subjects with uncompensated hypothyroidism (abnormally high thyroid-stimulating hormone (TSH) and abnormally low T4) or vitamin B12 deficiency (abnormally low) within the last 3 months prior to entry.
研究组 & 干预措施
Group 1
IGIV-C
干预措施: Immune Globulin IV (Human), 10% Caprylate/Chromatography Purified (Drug)
Group 2
干预措施: Albumin (Human) 25%, United States Pharmacopeia (USP) (Drug)
结局指标
主要结局
Comparison of the Responder Rates Between Two Treatment Groups in the Efficacy Period
时间窗: 6 months
The primary efficacy objective was the comparison of IGIV-C and Placebo group Responder rates. An Efficacy Period Responder was defined as a subject with ≥ 1 point improvement in the adjusted Inflammatory Neuropathy Case And Treatment (INCAT) score, with the improvement maintained through the end of Week 24 in the Efficacy Period. Measurements are reported in INCAT scale of 0-5 in both lower and upper extremities, for a total score of 0 to 10. INCAT scores for arm disability: 0 = no upper limb problems; 5 = inability to use either arm for any purposeful movement. INCAT scores for leg disability: 0= walking not affected; 5 = restricted to wheelchair, unable to stand and walk a few steps with help
次要结局
- Mean Change in the Amplitude (Millivolts) in the Most Severely Affected Motor Nerve During the Efficacy Period(6 months)
- Mean Change in Grip Strength During the Efficacy Period(6 months)
- Time to Relapse for Subjects Who Were IGIV-C Responders or IGIV-C Rescue Successes, During the Randomized Withdrawal Period(6 months)