Clinical Trial

. 2016 May:48:70-5.

doi: 10.1016/j.cct.2016.04.002. Epub 2016 Apr 11.

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)

Adriana H Tremoulet¹, Sonia Jain², Susan Kim³, Jane Newburger⁴, Moshe Arditi⁵, Alessandra Franco⁶, Brookie Best⁷, Jane C Burns⁸

Affiliations

¹ 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.
² Biostatistics Research Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
³ Rheumatology Program, Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Cardiology, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Children's Hospital of Boston, Boston, MA, USA.
⁵ Department of Pediatrics, Cedars Sinai Medical Center, USA; UCLA School of Medicine, USA.
⁶ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
⁷ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy, La Jolla, CA, USA.
⁸ 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.

PMID: 27080929
PMCID: PMC5221485
DOI: 10.1016/j.cct.2016.04.002

Clinical Trial

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)

Adriana H Tremoulet et al. Contemp Clin Trials. 2016 May.

. 2016 May:48:70-5.

doi: 10.1016/j.cct.2016.04.002. Epub 2016 Apr 11.

Authors

Adriana H Tremoulet¹, Sonia Jain², Susan Kim³, Jane Newburger⁴, Moshe Arditi⁵, Alessandra Franco⁶, Brookie Best⁷, Jane C Burns⁸

Affiliations

¹ 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.
² Biostatistics Research Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
³ Rheumatology Program, Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Cardiology, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Children's Hospital of Boston, Boston, MA, USA.
⁵ Department of Pediatrics, Cedars Sinai Medical Center, USA; UCLA School of Medicine, USA.
⁶ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
⁷ Department of Pediatrics, University of California San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy, La Jolla, CA, USA.
⁸ 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.

PMID: 27080929
PMCID: PMC5221485
DOI: 10.1016/j.cct.2016.04.002

Abstract

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.

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Figures

**Figure 1**
Study design and flow LAD, left anterior descending coronary artery; RCA, right coronary artery; IVIG, intravenous immunoglobulin; WBC, white blood cell count; hsCRP, high sensitivity C-reactive protein; ESR, erythrocyte sedimentation rate; PK, pharmacokinetic

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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)

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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)

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