# Safety and Dose Optimization of High-Dose Anakinra in Kawasaki Disease

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $174,906

## Abstract

Project Summary
Despite therapy with intravenous immunoglobulin (IVIG) plus infliximab, a monoclonal antibody against the pro-
inflammatory cytokine tumor necrosis factor (TNF) α, more than 25% of children with Kawasaki disease (KD),
the most common cause of acquired heart disease in children, develop coronary artery abnormalities (CAA)
with either dilated or aneurysmal coronary arteries. Once aneurysms have formed, the damage to the arterial
wall is irreversible, and over time, stenoses and calcification may lead to ischemic complications. However,
there is no recommended therapy to halt the progression of arterial wall damage and prevent aneurysm
formation. Thus, the goal of our project is to test a new therapy to attenuate CAA and block progression
of early injury to aneurysm formation.
In KD, the IL-1 pathway is upregulated, as demonstrated by increased transcript abundance by microarray and
by increased levels of pathway proteins in the plasma. In the Lactobacillus casei cell wall extract KD mouse
model of coronary arteritis, the IL-1 receptor antagonist, anakinra, prevented the development of CAA, as did
knocking out the IL-1 receptor. Given the role of the IL-1 pathway in KD-associated inflammation,
blockade of IL-1 with anakinra is a logical therapy to attenuate CAA in KD. Treatment with anakinra has
been well-tolerated and has coincided with a decrease in systemic inflammation and CAA in a small number of
KD patients. However, despite its increasing off-label use, there are limited data in infants and young children.
The proposed Phase I/IIa, dose escalation study will determine if anakinra in children at least 8 months to 17
years of age treated with IVIG and aspirin who have evidence of CAA by echocardiography is safe and well-
tolerated (Specific Aim 1). Furthermore, this study will evaluate if anakinra has high bioavailability and whether
its pharmacokinetics can be characterized by a one-compartment model using sparse sampling (Specific Aim
2). Lastly, this study will develop a pharmacodynamic biomarker-based model to find the proper dose of
anakinra for a sustained anti-inflammatory effect in children with acute KD and CAAs. (Specific Aim3).
Understanding the safety, PK, and proper dosing of anakinra to have a sustained anti-inflammatory
effect are central to moving forward with a Phase III study and addressing the unmet clinical need of
preventing formation or progression of aneurysms in KD.

## Key facts

- **NIH application ID:** 9970236
- **Project number:** 5P50HD090259-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ADRIANA H TREMOULET
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,906
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970236

## Citation

> US National Institutes of Health, RePORTER application 9970236, Safety and Dose Optimization of High-Dose Anakinra in Kawasaki Disease (5P50HD090259-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970236. Licensed CC0.

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