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)

Contemp Clin Trials. 2016 May;48:70-5. doi: 10.1016/j.cct.2016.04.002. Epub 2016 Apr 11.


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 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.

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 ≥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).

Conclusion: 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.

Trial registration: Clinical Trials.gov # NCT02179853, registered June 28, 2014.

Keywords: Anakinra; Coronary artery aneurysm; Interleukin 1; Kawasaki disease.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Child, Preschool
  • Coronary Aneurysm / etiology
  • Coronary Aneurysm / prevention & control*
  • Coronary Vessels / pathology*
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use
  • Infant
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Mucocutaneous Lymph Node Syndrome / complications
  • Mucocutaneous Lymph Node Syndrome / drug therapy*
  • Mucocutaneous Lymph Node Syndrome / pathology
  • Organ Size


  • Antirheumatic Agents
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Interleukin 1 Receptor Antagonist Protein

Associated data

  • ClinicalTrials.gov/NCT02179853