CLINICAL TRIAL: RITUXIMAB IN SUBJECTS WITH MODERATE TO SEVERE SYSTEMIC LUPUS ERY

临床试验：利妥昔单抗治疗中度至重度系统性狼疮患者

• 批准号: 7717881
• 负责人: ELIZA F CHAKRAVARTY
• 金额: $ 0.09万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717881
• 关键词: 6-Mercaptopurine; Adrenal Cortex Hormones; Antimalarials; Area Under Curve; Azathioprine; B-Lymphocytes; Chloroquine; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Daily; Disease; Dose; Double-Blind Method; Drug Kinetics; Elements; End Point; Enrollment; Flare; Funding; Grant; Great Britain; Health Surveys; Hydroxychloroquine; Immunosuppressive Agents; Infusion procedures; Institution; Intravenous; Label; Laboratories; Lower Limit of Normal; Lupus; Measures; Medlone 21; Methotrexate; Multicenter Studies; Oral; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Prednisone; Protocols documentation; Quality of life; Randomized; Recovery; Research; Research Personnel; Resources; Retreatment; SF-36; Safety; Score; Screening procedure; Source; Systemic Lupus Erythematosus; Time; United States; United States National Institutes of Health; Week; base; day; design; improved; indexing; mycophenolate mofetil; response; rituximab; 6-Mercaptopurine; Adrenal Cortex Hormones; Antimalarials; Area Under Curve; Azathioprine; B-Lymphocytes; Chloroquine; Clinical; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Daily; Disease; Dose; Double-Blind Method; Drug Kinetics; Elements; End Point; Enrollment; Flare; Funding; Grant; Great Britain; Health Surveys; Hydroxychloroquine; Immunosuppressive Agents; Infusion procedures; Institution; Intravenous; Label; Laboratories; Lower Limit of Normal; Lupus; Measures; Medlone 21; Methotrexate; Multicenter Studies; Oral; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Prednisone; Protocols documentation; Quality of life; Randomized; Recovery; Research; Research Personnel; Resources; Retreatment; SF-36; Safety; Score; Screening procedure; Source; Systemic Lupus Erythematosus; Time; United States; United States National Institutes of Health; Week; base; day; design; improved; indexing; mycophenolate mofetil; response; rituximab

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PRIMARY OBJECTIVE The primary objective of this study is to assess the efficacy of rituximab compared with placebo in achieving and maintaining a major clinical response (MCR) or partial clinical response (PCR) in subjects with moderate to severe systemic lupus erythematosus (SLE). SECONDARY OBJECTIVES The secondary objectives of this study (comparing rituximab with placebo) will be to evaluate the following: o Ability of rituximab to decrease overall SLE disease activity as measured by time-adjusted area under the curve minus baseline (AUCMB) scoring with the British Isles Lupus Assessment Group (BILAG) assessment over 52 weeks o Ability of rituximab to induce MCRs (excluding PCRs) or PCRs (including MCRs) o Safety and tolerability of rituximab o Ability of rituximab-treated subjects to achieve a BILAG C or better at Week 24 o Ability of rituximab to prolong the time to a moderate or severe flare o Ability of rituximab to improve quality of life as measured by SLE Expanded Health Survey (SF-36 index with additional elements specific to lupus) o Corticosteroid-sparing in subjects receiving rituximab o Pharmacokinetics of rituximab in subjects with SLE STUDY DESIGN This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab compared with placebo when combined with a single stable background immunosuppressive medication in subjects with moderate to severe SLE. The primary efficacy endpoint of the trial will be evaluated at 52 weeks. The study will enroll approximately 250 subjects at approximately 55 centers in the United States. Subjects will be randomized in a 2:1 ratio to receive rituximab + prednisone or placebo + prednisone. Randomized subjects will receive intravenous (IV) study drug + 2 separated by 15 days that is repeated at 6 months. In addition, subjects will receive 100 mg IV solumedrol 30-60 minutes prior to each study drug (rituximab or placebo) infusion. At entry, subjects must have a BILAG A score in one or more domains or a BILAG B score in two or more domains. Concomitant medications required are azathioprine, 6-mercaptopurine, mycophenolate mofetil (MMF), or methotrexate (MTX); plus prednisone and antimalarials (hydroxychloroquine or chloroquine). After screening, eligible subjects will receive daily oral prednisone (0.5 mg/kg, 0.75 mg/kg, or 1.0 mg/kg), based on their BILAG score and prestudy prednisone dose. Subjects will be assigned a prespecified prednisone taper starting on Day 16 for 10 weeks until a prednisone dose of = 10 mg/day is reached. After 10 weeks, subjects will continue to taper their corticosteroid as tolerated to a target dose of = 5 mg/day to Week 52. After Week 52, eligible subjects may enter an open-label retreatment study (under a separate protocol). Subjects who do not enter the retreatment study will be followed for at least 52 weeks after their last dose of study drug at Week 26. Subjects who do not enter the retreatment study will be followed by the investigator until Week 78 or until B-cell recovery, whichever is longer. B-cell recovery is defined as B-cell levels that have returned to baseline (Day 1) or to the lower limit of normal, as defined by the central laboratory.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 主要目标 这项研究的主要目的是评估利妥昔单抗与安慰剂在实现和维持主要临床反应（MCR）或部分临床反应（PCR）中的疗效（PCR）中中度至重度全身性红斑狼疮（SLE）。 次要目标 这项研究的次要目标（将利妥昔单抗与安慰剂进行比较）是评估以下内容： o利妥昔单抗在52周内通过不列颠群岛狼疮评估组（BILAG）评估的曲线减去基线（AUCMB）评分来降低总体调整区域的总体SLE疾病活动的能力 o利妥昔单抗诱导MCR（不包括PCR）或PCR（包括MCR）的能力 o利妥昔单抗的安全性和耐受性 o利妥昔单抗治疗的受试者在第24周获得BILAG C或更高的能力 o利妥昔单抗将时间延长到中等或重度耀斑的能力 o利妥昔单抗通过SLE扩展的健康调查衡量的能力改善生活质量（SF-36指数，具有特定于狼疮的其他元素） o接受利妥昔单抗的受试者的皮质类固醇比较 o SLE受试者利妥昔单抗的药代动力学 研究设计 这是一项II/III期，随机，双盲，安慰剂对照，多中心研究，可评估利妥昔单抗与安慰剂相比，与安慰剂相比，与单个稳定的背景免疫抑制药物相比，在中度至重度SLE的受试者中。试验的主要功效终点将在52周内评估。该研究将在美国约55个中心招收约250名受试者。受试者将以2：1的比率随机分配，以接收利妥昔单抗 +泼尼松或安慰剂 +泼尼松。随机受试者将接受静脉内（IV）研究药物 + 2分隔15天，在6个月时重复。此外， 受试者将在每种研究药物（利妥昔单抗或安慰剂）输注前30-60分钟接受100 mg静脉注射。 进入时，受试者必须在一个或多个域或两个或多个域中的Bilag B分数中获得BILAG分数。所需的伴随药物是硫唑嘌呤，6-羟基托嘌呤，霉酚酸酯（MMF）或甲氨蝶呤（MTX）；加上泼尼松和抗菌素（羟氯喹或氯喹）。筛选后，符合条件的受试者将根据其BILAG评分和陈述性泼尼松剂量接受每日口服泼尼松（0.5 mg/kg，0.75 mg/kg或1.0 mg/kg）。从第16天开始，将分配受试者预先指定的泼尼松锥度10周，直到达到10 mg/天的泼尼松剂量。 10周后，受试者将继续缩减皮质类固醇，以耐受性剂量为= 5 mg/天到第52周。第52周后，符合条件的受试者可以进入开放标签的撤退研究（根据单独的协议）。未进入撤退研究的受试者将在第26周的最后一剂研究药物后至少进行52周。未进入撤退研究的受试者将在第78周或直到B细胞恢复（以较长者为准）后面进行研究人员。 B细胞恢复定义为B细胞水平已返回基线（第1天）或正常的下限，如中央实验室所定义。