title: Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial).
abstract: 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 IVIG 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.
  
  
  
  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.
  
  
  
  This is a two-center dose-escalation Phase I/IIa trial in 30 acute KD patients ≥8months 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).
  
  
  
  The safety and tolerability of blocking both IL-1α and Il-1β by anakinra will be evaluated as a strategy to prevent or attenuate coronary artery damage in infants and children with acute KD.
  
  
  
  Clinical Trials.gov # NCT02179853, registered June 28, 2014.
authors.affiliation: Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Rady Children's Hospital San Diego, San Diego, CA, USA. Electronic address: atremoulet@ucsd.edu.
authors.forename: Adriana H
authors.initials: AH
authors.lastname: Tremoulet
authors.affiliation: Biostatistics Research Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Rheumatology Program, Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Children's Hospital of Boston, Boston, MA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Newburger
authors.affiliation: Department of Pediatrics, Cedars Sinai Medical Center, USA; UCLA School of Medicine, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franco
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy, La Jolla, CA, USA.
authors.forename: Brookie
authors.initials: B
authors.lastname: Best
authors.affiliation: Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Rady Children's Hospital San Diego, San Diego, CA, USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Burns
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size
chemical_list: D018501:Antirheumatic Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein
keywords: Anakinra; Coronary artery aneurysm; Interleukin 1; Kawasaki disease