Etanercept for Acute Kawasaki Disease IND 101,223

依那西普治疗急性川崎病 IND 101,223

• 批准号: 7567634
• 负责人: Michael A Portman
• 金额: $ 40万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7567634
• 关键词: Etanercept; Acute; Kawasaki; Disease; IND

DESCRIPTION (provided by applicant): Kawasaki Disease (KD) or Syndrome is the leading cause of acquired heart disease in children the United States. The Center for Disease Control estimates that over 4000 U.S. children per year are diagnosed with KD. Although, KD qualifies for Orphan Disease status by NIH and FDA standards, it is a growing and important health problem for children in the U.S. and worldwide. KD is an autoimmune disease and includes vasculitis with a specific predilection for coronary arteries, causing aneurysm and/or ectasia. Although, the majority of patients do well, many experience long term coronary artery abnormalities. Treatment with intravenous immunoglobulin (IVIG) and aspirin currently represents the standard of care for acute Kawasaki Disease. New and emerging data show that this treatment is only partially effective for reducing the risk of coronary artery disease. Additionally, KD in many patients demonstrates resistance or refractoriness to IVIG, and requires retreatment. This refractoriness represents a primary risk factor for development of coronary artery dilation. Attempts at developing effective adjunctive therapy for IVIG and aspirin have failed. Over the past 15-20 years, multiple investigators have provided strong evidence implicating tumor necrosis-a (TNF-a) as a primary agent for inflammation in acute KD. TNF-a antagonism with etanercept abrogates coronary artery disease in a validated mouse model of KD. Etanercept is FDA approved for multiple indications in adults and in children down to four years of age for juvenile rheumatoid arthritis (JRA). This investigator performed a pilot study in acute KD patients (age 6 months to 5 years). In this population, it was demonstrated that etanercept (0.8 mg/kg) given subcutaneously at weekly intervals in 3 doses provides serum concentrations within the therapeutic range for JRA patients. The results of the pilot study support the safety of etanercept in young children and show promise for efficacy in reducing IVIG resistance. The investigator plans to test the hypothesis that TNF-a antagonism with etanercept improves the clinical response to standard of care treatment with IVIG and aspirin therapy in KD patients between 2 months and 20 years of age. To test this hypothesis a double-blinded placebo controlled trial in 220 children with KD will be performed and data will be obtained in order to achieve an orphan designation for etanercept.

描述（由申请人提供）： 在美国，川崎或川崎综合征是儿童获得性心脏病的主要原因。疾病控制中心估计，每年有超过4000名美国儿童被诊断患有KD。虽然KD符合NIH和FDA标准的孤儿病状态，但它是美国和全球儿童日益严重的健康问题。KD是一种自身免疫性疾病，包括血管炎，特别是冠状动脉，导致动脉瘤和/或扩张。虽然大多数患者情况良好，但许多患者经历了长期的冠状动脉异常。静脉注射免疫球蛋白（IVIG）和阿司匹林治疗目前代表了急性川崎病的标准治疗。新的和正在出现的数据表明，这种治疗对降低冠状动脉疾病的风险仅部分有效。此外，许多患者的KD表现出对IVIG的耐药性或不应性，需要重新治疗。这种难治性是冠状动脉扩张的主要危险因素。 开发IVIG和阿司匹林的有效连续治疗的尝试失败了。在过去的15-20年中，许多研究者提供了强有力的证据，表明肿瘤坏死因子-α（TNF-α）是急性KD炎症的主要因素。用依那西普拮抗TNF-α在KD的经验证的小鼠模型中消除冠状动脉疾病 依那西普被FDA批准用于成人和4岁以下儿童的多种适应症，用于治疗幼年型类风湿性关节炎（JRA）。 该研究者在急性KD患者（年龄6个月至5岁）中进行了一项初步研究。在该人群中，已证明依那西普（0.8 mg/kg）每周皮下给药一次，分3次给药，可使JRA患者的血清浓度在治疗范围内。初步研究的结果支持依那西普在幼儿中的安全性，并显示出减少IVIG抵抗的有效性。研究者计划检验以下假设：在2个月至20岁之间的KD患者中，用依那西普进行TNF-α拮抗可改善对IVIG和阿司匹林治疗的标准治疗的临床应答。为了检验这一假设，将在220名KD儿童中进行一项双盲安慰剂对照试验，并将获得数据，以实现依那西普的孤儿药认定。