MONOCLONAL ANTI-BLYS ANTIBODY IN SUBJECTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。目的：¿研究设计：本研究是一项在活动性系统性红斑狼疮（SLE）受试者中进行的II期、多中心、安慰剂对照、平行设计、剂量范围确定的52周研究。该研究旨在评价SLE受试者静脉内（IV）给予3种不同剂量（1.0、4.0和10.0 mg/kg）的DaphoStat-B的安全性、耐受性和疗效。受试者将被随机分配到4个治疗组中的一个，然后通过筛选时的SELENA SLEDAI评分（4 - 7 vs. > 8）进行分层。最多将入组350例SLE受试者，每个治疗组的目标为80例受试者。 所有受试者将在第0、14和28天接受给药，然后在52周的剩余时间内每28天接受一次给药。所有治疗将在至少2小时输注期内IV给药。对于有过敏史或食物、药物或昆虫过敏反应史或荨麻疹史的受试者，建议其在给药前接受苯海拉明（12.5 - 50 mg，基于临床判断）和对乙酰氨基酚治疗。 完成52周治疗期的受试者可选择在24周扩展期内继续接受当前剂量。接受安慰剂或接受活性研究药物但无满意应答的受试者（即，在第52周时，SELENA SLEDAI或BILAG疾病活动性评分改善或SLE发作频率或严重程度降低）可在24周延长期内接受最高耐受剂量的AlphoStat-B。治疗52周或完成24周扩展期后，所有受试者将完成研究，但返回接受8周和24周随访访视。本临床试验将成立内部数据监查委员会（DMC）。DMC可能包括流变学领域的外部专家和外部统计学家。DMC将在研究开始后约3个月或前100例受试者入组后（以先发生者为准）审查安全性。初始安全性审查将以设盲方式进行。除非审查中出现安全性信号，否则不会对试验数据揭盲。初步审查后，委员会将每季度审查一次数据。当所有受试者完成24周研究时，委员会将以非盲方式审查24周分析的安全性和疗效结果。在随后的安全性审查（至少每季度一次）中，DMC将以非盲方式审查安全性数据。

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. OBJECTIVES: ¿ To evaluate the safety and tolerability of LymphoStat-B ¿ To evaluate the efficacy of LymphoStat-B STUDY DESIGN: This study is a Phase II, multicenter, placebo-controlled, parallel-design, dose-ranging 52-week study of LymphoStat-B in subjects with active systemic lupus erythematosus (SLE). The study is designed to evaluate the safety, tolerability, and efficacy of 3 different doses (1.0, 4.0, and 10.0 mg/kg) of intravenously (IV) administered LymphoStat-B in subjects with SLE. Subjects will be randomly assigned, following stratification by the screening SELENA SLEDAI score (4 to 7 vs. > 8), to one of the 4 treatment groups. A maximum of 350 SLE subjects will be enrolled, with a target of 80 subjects per treatment group. All subjects will be dosed on days 0, 14, and 28, then every 28 days for remainder of the 52 weeks. All treatments will be administered IV over a minimum 2-hr infusion period. For subjects with a history of allergies, or allergic responses to food, drugs, or insects, or a history of urticaria, it is suggested that they receive Diphenhydramine (12.5 to 50 mg based on clinical judgment) and Acetaminophen prophylactically prior to dosing. Subjects who complete the 52-week treatment period will then be given the option to continue at their current dose during a 24-week extension period. Subjects who received placebo or who received active study agent without a satisfactory response (i.e., improvement in SELENA SLEDAI or BILAG disease activity score or reduction in frequency or severity of SLE flare at week 52) may receive the highest tolerable dose of LymphoStat-B during the 24-week extension period. After 52 weeks of treatment or completion of the 24-week extension period, all subjects will complete the study, but return for an 8-wk and 24-week follow-up visit. There will be an internal Data Monitoring Committee (DMC) for this clinical trial. The DMC may include outside experts in the field of rheumatology and an external statistician. The DMC will review safety approximately 3 months after the initiation of the study or after the first 100 subjects have been enrolled, whichever comes first. The initial safety review will be performed in a blinded fashion. Data from the trial will not be unblinded unless there are safety signals arising from the review. After the initial review, the committee will review the data quarterly. When all subjects have completed 24 weeks on study, the committee will review both safety and efficacy results from the 24-week analyses in an unblinded manner. In subsequent safety reviews, held at least quarterly, the DMC will review the safety data in an unblinded fashion.