期刊
CONTEMPORARY CLINICAL TRIALS
卷 48, 期 -, 页码 70-75出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cct.2016.04.002
关键词
Anakinra; Interleukin 1; Kawasaki disease; Coronary artery aneurysm
资金
- University of California San Diego Department of Pediatrics Intramural Clinical Research grant
- Rady Children's Hospital San Diego Academic Enrichment grant
- Gordon and Marilyn Macklin Foundation grant
- Clinical and Translational Study Unit at Boston Children's Hospital
Background: Although Kawasaki disease (KD) is the most common cause of acquired heart disease in children and may result in coronary artery aneurysms (CAA) with an attendant risk of myocardial infarction, there is no recommended therapy to halt progression of arterial wall damage and prevent aneurysm formation in the acute phase of the vasculitis. While intravenous immunoglobulin (IVIG) reduces the risk of CAA, up to 20% of KD patients are MG resistant and have a higher risk for developing CAA. The IL-1 pro-inflammatory pathway is upregulated in children with acute KD and plays a critical role in the experimental animal model of KD. Thus, IL-1 is a logical therapeutic target. Objectives: The goal of this study is to determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of anakinra, a recombinant human IL-1 receptor antagonist, in acute KD patients with coronary artery abnormalities on the baseline echocardiogram. Design: This is a two-center dose-escalation Phase I/IIa trial in 30 acute KD patients >= 8 months old with a coronary artery Z score >= 3.0 in the right coronary artery and/or left anterior descending artery or an aneurysm. Subjects will receive a 2- to 6-week course of anakinra by daily subcutaneous injection and will be assessed for resolution of inflammation and dose limiting toxicities (leukopenia, anaphylactoid reaction, or severe infection). Conclusion: The safety and tolerability of blocking both IL-1 alpha, and Il-1 beta, by anakinra will be evaluated as a strategy to prevent or attenuate coronary artery damage in infants and children with acute KD. (C) 2016 Elsevier Inc. All rights reserved.
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