Etanercept for Acute Kawasaki Disease IND 101,223

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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.