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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。系统性幼年特发性关节炎（S-JIA）约占所有儿童JIA病例的10%至20%。JIA的病因尚不清楚。目前，对于S-JIA患儿尚无最佳治疗方法。白细胞介素-1 （IL-1）已被证明是参与活性S-JIA的关键炎症分子。这是一项I期中试研究，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患儿疾病表现的有效性。这项研究将在多达10个中心进行，并招募18名年龄在4-21岁之间、诊断为S-JIA的受试者。前9名受试者将接受为期4周的每周注射2.2 mg/kg IL-1诱捕剂（6名受试者）或安慰剂（3名受试者）。像注射胰岛素一样，注射到皮肤下的组织（皮下）。在对最初的安全性数据进行评估后，如果2.2 mg/kg的剂量似乎是安全的，接下来的9名受试者将被招募，并将接受4.4 mg/kg IL-1诱捕剂（6名受试者）或安慰剂（3名受试者），为期4周。在为期四周的研究中，临床工作人员的受试者都不知道谁服用了IL-1诱捕剂或安慰剂（盲法研究）。谁将接受IL-1诱捕剂或安慰剂将通过随机选择来决定。在完成4周的盲法研究后，所有参与者将接受为期13个月的开放标签IL-1陷阱治疗。在这项研究中，将抽取血液来测量IL-1陷阱的水平，以显示IL-1陷阱在系统性JIA患儿体内的峰值水平和消除速度。这些信息将用于观察成人和儿童IL-1诱捕剂的水平是否相似。此外，本研究的信息可用于计划对系统性JIA患儿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.