STUDY OF TACI-FC5 ADMINISTERED TO PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

TACI-FC5 治疗系统性红斑狼疮患者的研究

• 批准号: 7375268
• 负责人: MARK C GENOVESE
• 金额: $ 2.54万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375268
• 关键词: STUDY; TACI; FC5; ADMINISTERED; PATIENTS

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: ¿ The purpose of this research study is to assess the safety, tolerability, and effectiveness of a single dose of this investigational agent which is being studied for the treatment of systemic lupus erythematosus (SLE). ¿ To characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of TACI-Fc5 in SLE patients following a single subcutaneous dose, and to monitor its effects on selected biological markers of disease activity. STUDY DESIGN: Thirty-two male and female patients will be included (as 4 cohorts of 8). Each will undergo assessment at a pre-study visit within 14 days before administration of the investigational product, and will receive a single subcutaneous dose of TACI-Fc5 or corresponding placebo. Up to four doses of TACI-Fc5 will be assessed. The first cohort will be administered a single subcutaneous dose of TACI-Fc5 at a dose of 0.3 mg/kg. Subsequent cohorts will receive doses based upon the dose-escalation decision algorithm, up to a maximal dose of 9 mg/kg. Patients will attend the clinic on the day of investigational medicinal product administration (Study Day 1) and remain resident until after the 12 hr Pharmacokinetic/Pharmacodynamic blood samples have been collected. They will return to the clinic on an outpatient basis for post-dose procedures that include collection of pharmacokinetic and pharmacodynamic samples and safety assessments conducted at pre-defined intervals up to 6 weeks following dosing. A post-study visit is scheduled to take place 6 weeks (¿ 2 days) following dosing. STUDY POPULATION AND MAIN ELIGIBILITY CRITERIA: Male and female patients aged 18 to 70 yrs with proven diagnosis of SLE with at least 4 of the ACR criteria at the time of screening and SLE disease activity index (SELENA SLEDAI) score 0 - 8. Thirty-two patients will be expected, distributed between 3 US study sites. INVESTIGATIONAL PRODUCT: The liquid formulation of TACI-Fc5 will be provided in vials filled to deliver 0.5 mL and containing 70 mg of TACI-Fc5. The placebo will be provided in vials filled to deliver 0.5 mL SQ. DATA ANALYSIS AND STATISTICS: The primary objective of the study is to perform an assessment of the systemic and local tolerability of TACI-Fc5 in patients with SLE. This will be achieved through monitoring of: vital signs, ECGs and laboratory parameters (including hematology, coagulation, clinical chemistry and urinalysis). Close monitoring of adverse events will be conducted throughout the study in addition to regular assessments of the injection site for evidence of localized reactions. The secondary objective of the study is to characterize the pharmacokinetics and pharmacodynamics of TACI-Fc5 in SLE patients and to monitor the effects on the biological markers of disease activity. Additional biological markers endpoints of the study will be the assessment of lymphocyte subsets, serum concentrations of free BLyS, BLyS/TACI-Fc5 complex, IgG and IgM and anti-dsDNA antibodies up to 6 weeks post-dose. Serum levels of anti-TACI-Fc5 antibodies will be measured at pre-dose on day 1 and at the post-study visit. The assessment will include the evaluation over time and change from baseline for all the markers above.

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，不一定是研究者所在机构。目的：¿本研究的目的是评估单次给药该研究药物治疗系统性红斑狼疮（SLE）的安全性、耐受性和有效性。研究SLE患者单次皮下注射泰爱Fc 5后的药代动力学（PK）和药效学（PD），并监测其对选定的疾病活动生物标志物的影响。 研究设计：将纳入32例男性和女性患者（作为4个队列，每组8例）。每名受试者将在研究药物给药前14天内的研究前访视时接受评估，并将接受泰爱Fc 5或相应安慰剂单次皮下给药。将评估最多4剂泰爱Fc 5。第一个队列将接受0.3 mg/kg剂量的泰爱Fc 5单次皮下给药。后续队列将根据剂量递增决策算法接受剂量，最高剂量为9 mg/kg。患者将在试验用药品给药当天（研究第1天）到诊所就诊，并在采集12小时药代动力学/药效学血样后继续住院。他们将以门诊方式返回诊所进行给药后程序，包括收集药代动力学和药效学样本以及在给药后6周内以预定间隔进行安全性评估。计划在给药后6周（约2天）进行研究后访视。 研究人群和主要入选标准：年龄18 - 70岁的男性和女性患者，在筛选时至少符合4项ACR标准，SLE疾病活动指数（SELENA SLEDAI）评分为0 - 8。预计将有32例患者分布在3家美国研究中心。 预防性产品：泰爱-Fc 5液体制剂将以小瓶形式提供，灌装至0.5 mL，含70 mg泰爱-Fc 5。安慰剂将以小瓶形式提供，灌装至0.5 mL SQ。数据分析和统计：本研究的主要目的是评估泰爱Fc 5在SLE患者中的全身和局部耐受性。这将通过监测：生命体征、心电图和实验室参数（包括血液学、凝血、临床生化和尿液分析）来实现。除了定期评估注射部位局部反应的证据外，还将在整个研究期间密切监测不良事件。本研究的次要目的是描述泰爱Fc 5在SLE患者中的药代动力学和药效学特征，并监测其对疾病活动性生物标志物的影响。本研究的其他生物标志物终点将是淋巴细胞亚群、游离BLyS、BLyS/泰爱-Fc 5复合物、IgG和IgM以及抗dsDNA抗体的血清浓度评估，直至给药后6周。将在第1天给药前和研究后访视时测量抗TACI-Fc 5抗体的血清水平。评估将包括随时间推移的评价以及上述所有标志物相对于基线的变化。