Anakinra in Infants and Children With Coronary Artery Abnormalities in Acute Kawasaki Disease
Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the developed world. Despite available treatment, 25% of children in San Diego County appropriately treated for KD develop coronary artery abnormalities that may lead to complications later in life, including heart attack. Although the investigators can identify children with KD that have these coronary artery abnormalities, there is no approved additional treatment to decrease coronary artery inflammation and arrest or prevent damage to the coronary arteries. Anakinra, a therapy that blocks the high levels of interleukin 1 (IL1) that lead to inflammation during acute KD, has been shown in the KD mouse model to prevent the development of coronary artery damage. Therefore, the investigators propose to study the safety and activity of anakinra in infants and children < 2 years old with coronary artery abnormalities from KD.
Arms and Interventions
This is a dose escalation study (4 mg/kg, 6 mg/kg and 8 mg/kg).
First two doses IV followed by SQ dosing
Primary Outcome Measures
- Safety of a 2 or 6 week course of anakinra [2 to 6 weeks]
The safety of anakinra will be assessed by monitoring for clinical and laboratory signs of infection and injection site reactions.
Secondary Outcome Measures
- Activity of anakinra for 6 weeks [At baseline, 2 weeks and 6 weeks]
Blood will be tested pre-drug administration, at 2 weeks and at 6 weeks for markers of inflammation and enumeration of regulatory T-cells. Echocardiographic assessment of coronary arteries at these time points will be compared to historical controls matched for age, sex and coronary artery status on initial echo.
Infant or child aged 1 month to 17 years, who meets clinical criteria for KD according to American Heart Association guidelines (Table 2): Fever (T≥38oC or 100.4oC) ≥ 3 days and ≥ 2 clinical criteria with left anterior descending (LAD)/right coronary artery (RCA) Z score ≥ 3.0 or an aneurysm (≥ 1.5 x the adjacent segment) of one of the coronary artery segments
Patient presents within the first 20 days after fever onset
Parent or legal guardian able and willing to provide informed consent; adolescent or child assent as appropriate
Post-menarchal females: Negative pregnancy test at screening and willing to use two forms of contraception during the study
Males engaging in sexual activity that could lead to pregnancy willing to use a condom.
Use of an IL-1 antagonist within the 3 months prior to enrollment
History of chronic disease, except asthma, atopic dermatitis, autism or controlled seizure disorder
History of hypersensitivity to anakinra
History of tuberculosis (TB) or TB exposure
Contacts and Locations
|Rady Children's Hospital San Diego
Sponsors and Collaborators
- University of California, San Diego
- Boston Children's Hospital
- Cedars-Sinai Medical Center
- Principal Investigator: Adriana H Tremoulet, MD, UCSD
- Study Director: Jane C Burns, MD, UCSD
Study Documents (Full-Text)None provided.
- KD Anakinra