TOLERABILITY AND PRELIMINARY EFFICACY STUDY OF TWO DOSE LEVELS OF IL-1 TRAP

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。全身性幼年特发性关节炎（S-JIA）约占儿童JIA所有病例的10%至20%。JIA的病因不明。目前，对于S-JIA儿童还没有最佳的治疗方法。白细胞介素-1（IL-1）是参与活动性S-JIA的关键炎症分子。这是一项I期初步研究，旨在确定IL-1 Trap（一种新的每周抗IL-1药物）的合适剂量，评估IL-1 Trap的安全性，以及其改善S-JIA儿童疾病表现的有效性。 本研究将在多达10家临床试验机构进行，入组18例年龄在4-21岁之间的诊断为S-JIA的受试者。入组的前9名受试者将接受每周注射2.2 mg/kg IL-1 Trap（6名受试者）或安慰剂（3名受试者），持续4周。注射是在皮肤下的组织（皮下），就像胰岛素注射一样。在评价初始安全性数据后，如果2.2 mg/kg剂量似乎是安全的，则将入组接下来的9例受试者，并将接受4.4 mg/kg IL-1 Trap（6例受试者）或安慰剂（3例受试者）治疗4周。在研究的4周期间，诊所工作人员的受试者都不知道谁正在接受IL-1 Trap或安慰剂（设盲研究）。关于谁将接受IL-1陷阱或安慰剂的决定将通过随机选择来完成。在完成4周的设盲研究后，所有参与者将接受开放标签IL-1 Trap治疗13个月。在这项研究中，将抽取血液来测量IL-1陷阱的水平，以显示峰值水平以及它从全身性JIA儿童中消除的速度。该信息将用于观察给予IL-1 Trap的成人和儿童的IL-1 Trap水平是否相似。此外，本研究的信息可用于计划在系统性JIA儿童中进行更大规模的研究。

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. Systemic Juvenile Idiopathic Arthritis (S-JIA) represents about 10 to 20% of all cases of JIA in children. The cause of JIA is unknown. At this time, there is no optimal therapy for children with S-JIA. Interleukin-1 (IL-1) has been shown to be a key inflammatory molecule involved in active S-JIA. This is a Phase I pilot study to determine an appropriate dose of IL-1 Trap (a new weekly anti-IL-1 drug), evaluate the safety of IL-1 Trap, and its effectiveness in improving the disease manifestations in children with S-JIA. This is a study that will be performed in up to 10 centers and enroll 18 subjects between the ages of 4-21 with the diagnosis of S-JIA. The first 9 subjects enrolled will receive either weekly injections of either 2.2 mg/kg IL-1 Trap (6 subjects) or placebo (3 subjects) for 4 weeks. The injections are given into the tissue just under the skin (subcutaneous) like insulin injections. After evaluation of the initial safety data, if the 2.2 mg/kg dose appears to be safe, the next 9 subjects will be enrolled and will receive either 4.4 mg/kg IL-1 Trap (6 subjects) or placebo (3 subjects) for 4 weeks. During the 4 weeks of the study neither the subjects of the clinic staff will know who is getting the IL-1 Trap or placebo (a blinded study). The decision about who will receive the IL-1 Trap or placebo will be done by random selection. After completion of the 4 weeks of the blinded study, all participants will receive treatment with open label IL-1 Trap for 13 months. During this study, blood will be drawn to measure levels of IL-1 Trap to show the peak level and how quickly it is eliminated from children with Systemic JIA. This information will be used to see if the IL-1 Trap levels are similar in adult and children given IL-1 Trap. In addition, information from this study may be used in planning for a larger study in children with Systemic JIA.