Kawasaki Disease
Conditions
Keywords
Kawasaki disease, Anakinra, IL-1
Brief summary
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.
Interventions
DRUGAnakinra
First two doses IV followed by SQ dosing
Sponsors
Boston Children's Hospital
Cedars-Sinai Medical Center
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
1. 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 2. Patient presents within the first 20 days after fever onset 3. Parent or legal guardian able and willing to provide informed consent; adolescent or child assent as appropriate 4. Post-menarchal females: Negative pregnancy test at screening and willing to use two forms of contraception during the study 5. Males engaging in sexual activity that could lead to pregnancy willing to use a condom.
Exclusion criteria
1. Use of an IL-1 antagonist within the 3 months prior to enrollment 2. History of chronic disease, except asthma, atopic dermatitis, autism or controlled seizure disorder 3. History of hypersensitivity to anakinra 4. History of tuberculosis (TB) or TB exposure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | within 6 weeks of treatment | The primary outcome measure was the safety and tolerability of anakinra |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 (Anakinra 2-4 mg/kg/Day) Participants were administered 2-4 mg/kg/day of Anakinra intravenously every 12 hours for the first 24 hours and subsequently administered subcutaneously every 24 hours. | 4 |
| Dose Level 2 (Anakinra 5-7 mg/kg/Day) Participants were administered 5-7 mg/kg/day of Anakinra intravenously every 12 hours for the first 24 hours and subsequently administered subcutaneously every 24 hours. | 3 |
| Dose Level 3 (Anakinra 8-11 mg/kg/Day) Participants were administered 8-11 mg/kg/day of Anakinra intravenously every 12 hours for the first 24 hours and subsequently administered subcutaneously every 24 hours. | 15 |
| Total | 22 |
Baseline characteristics
| Characteristic | Dose Level 2 (Anakinra 5-7 mg/kg/Day) | Dose Level 3 (Anakinra 8-11 mg/kg/Day) | Total | Dose Level 1 (Anakinra 2-4 mg/kg/Day) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 15 Participants | 22 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 0.8 years | 1.2 years | 1.1 years | 1.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 10 Participants | 2 Participants |
| Region of Enrollment United States | 3 participants | 15 participants | 22 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 13 Participants | 18 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 15 |
| other Total, other adverse events | 2 / 4 | 3 / 3 | 13 / 15 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 | 0 / 15 |
Outcome results
Primary
Number of Participants With Adverse Events
The primary outcome measure was the safety and tolerability of anakinra
Time frame: within 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 (Anakinra 2-4 mg/kg/Day) | Number of Participants With Adverse Events | 2 participants |
| Dose Level 1 (Anakinra 5-7 mg/kg/Day) | Number of Participants With Adverse Events | 3 participants |
| Dose Level 3 (Anakinra 8-11 mg/kg/Day) | Number of Participants With Adverse Events | 13 participants |