Kawasaki Disease
Conditions
Brief summary
This study evaluates the safety of infliximab in infants and children with acute Kawasaki Disease.
Detailed description
This study is an exploratory, pilot study to examine tolerance and pharmacokinetics of infliximab in infants and children with acute Kawasaki Disease.
Interventions
Remicade was 5 mg/kg IV (single dose)
BIOLOGICALIntravenous immunoglobulin (IVIG)
2nd dose of IVIG (2g/kg)
Sponsors
Centocor, Inc.
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for the trial, subjects must meet all of the following criteria: 1. All eligible subjects, or legal representative, must provide written informed consent/assent, prior to initiation of any study procedure. 2. Eligible subjects will be infants and children, under 18 years old, with acute KD who remain or become febrile (\>/= 38.3˚ C or 101.0˚ F) after the end of the 48 h-period after completing their IVIG infusion (2gm/kg). 3. Patients must have persistent or reoccurrence of fever \> 48 hours of observation to be eligible for the trial. 4. Prior to the initial IVIG treatment, patients must have been febrile for \>/= 3 days and have met 4/5 standard clinical criteria (Table 1) - OR - patients with fever and 3/5 clinical criteria will be eligible if echocardiogram demonstrates at least one coronary artery segment with a Z score of \> 2. 5. Patients must present for their initial diagnosis and IVIG treatment within the first 14 days after fever onset (Illness Day 14). 6. Females of childbearing potential and males must be using adequate contraception (abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) throughout the trial. 7. All eligible subjects must have a chest radiograph within one week prior to first infusion of study drug with no evidence of malignancy, infection or fibrosis.
Exclusion criteria
If a subject has any of the following criteria, he or she may not be enrolled in the study: 1. Have been receiving corticosteroids (ie, via any route) at doses \> 1 mg/kg prednisone equivalent daily. 2. Have history of TB or TB exposure. 3. Have history of histoplasmosis or coccidiomycosis. 4. Have received anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 1 month prior to first study drug administration. 5. Have any chronic disease, except asthma, atopic dermatitis or controlled seizure disorder. 6. Have documented history of current active hepatitis B or a history of hepatitis C infection. 7. Have documented history of human immunodeficiency virus (HIV) infection 8. Have received a transplanted organ (with the exception of a corneal transplant performed \> 3 months prior to first study drug administration). 9. Have a known malignancy or history of malignancy within the 5-year period prior to first study drug administration (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence). 10. Have a history of prior lymphoproliferative disease including lymphoma. 11. Have multiple sclerosis or other central demyelinating disorder. 12. Have received any previous treatment with infliximab or other monoclonal antibodies. 13. Have used any investigational drug within 1 month prior to first study drug administration or within 5 half-lives of the investigational agent, whichever is longer. 14. Are participating in another investigative trial, involving investigational agents, during participation in this trial. 15. Have a history of substance abuse (drug or alcohol) within the previous 3 years. 16. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter. 17. Have a known allergy to murine proteins or other chimeric proteins. 18. Patients with ischemic congestive heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (Focused on Side Effects From IVIG or Infliximab Administration) | 2 weeks | The safety of giving infliximab to treat IVIG-resistant Kawasaki disease was measured by recording the number of adverse events that occurred in each group. An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of either IVIG or infliximab, regardless of whether it was considered related to IVIG or infliximab, that occured during the course of this study.In particular we evaluated for AEs related to side effects from infliximab or IVIG. |
| Area Under the Curve of Infliximab Concentration Before Infliximab Infusion and Then 2 and 24 Hours, 1 Week (5 to 9 Days), 2 Weeks (12 to 16 Days), and 4 Weeks (26 to 30 Days) After Infliximab Infusion) | before infliximab infusion and then 2 and 24 hours, 1 week (5 to 9 days), 2 weeks (12 to 16 days), and 4 weeks (26 to 30 days) after infliximab infusion. | The area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last) was estimated using the trapezoidal rule up to the last measurable concentration.Samples were collected before infliximab infusion and then at 2 and 24 hours, 1 week (5 to 9 days), 2 weeks (12 to 16 days), and 4 weeks (26 to 30 days) after infliximab infusion. Subjects with detectable infliximab concentrations at week 4 had another sample drawn at week 10 (68 to 72 days). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IVIG Arm (2 gr/kg) 2nd dose of IVIG (2gr/kg) | 12 |
| Infliximab (5mg/kg) Remicade (Infliximab Arm of 5mg/kg) | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Infliximab (5mg/kg) | IVIG Arm (2 gr/kg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 1.667 years STANDARD_DEVIATION 0.3 | 1.833 years STANDARD_DEVIATION 0.3 | 1.75 years STANDARD_DEVIATION 0.3 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 12 | 10 / 12 |
| serious Total, serious adverse events | 2 / 12 | 3 / 12 |
Outcome results
Primary
Area Under the Curve of Infliximab Concentration Before Infliximab Infusion and Then 2 and 24 Hours, 1 Week (5 to 9 Days), 2 Weeks (12 to 16 Days), and 4 Weeks (26 to 30 Days) After Infliximab Infusion)
The area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last) was estimated using the trapezoidal rule up to the last measurable concentration.Samples were collected before infliximab infusion and then at 2 and 24 hours, 1 week (5 to 9 days), 2 weeks (12 to 16 days), and 4 weeks (26 to 30 days) after infliximab infusion. Subjects with detectable infliximab concentrations at week 4 had another sample drawn at week 10 (68 to 72 days).
Time frame: before infliximab infusion and then 2 and 24 hours, 1 week (5 to 9 days), 2 weeks (12 to 16 days), and 4 weeks (26 to 30 days) after infliximab infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IVIG Arm (2 gr/kg) | Area Under the Curve of Infliximab Concentration Before Infliximab Infusion and Then 2 and 24 Hours, 1 Week (5 to 9 Days), 2 Weeks (12 to 16 Days), and 4 Weeks (26 to 30 Days) After Infliximab Infusion) | 0 micogram*day/ml |
| Infliximab (5mg/kg) | Area Under the Curve of Infliximab Concentration Before Infliximab Infusion and Then 2 and 24 Hours, 1 Week (5 to 9 Days), 2 Weeks (12 to 16 Days), and 4 Weeks (26 to 30 Days) After Infliximab Infusion) | 619 micogram*day/ml |
Primary
Number of Adverse Events (Focused on Side Effects From IVIG or Infliximab Administration)
The safety of giving infliximab to treat IVIG-resistant Kawasaki disease was measured by recording the number of adverse events that occurred in each group. An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of either IVIG or infliximab, regardless of whether it was considered related to IVIG or infliximab, that occured during the course of this study.In particular we evaluated for AEs related to side effects from infliximab or IVIG.
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IVIG Arm (2 gr/kg) | Number of Adverse Events (Focused on Side Effects From IVIG or Infliximab Administration) | 2 events |
| Infliximab (5mg/kg) | Number of Adverse Events (Focused on Side Effects From IVIG or Infliximab Administration) | 3 events |