A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease
Condition: Mucocutaneous Lymph Node Syndrome; Kawasaki Disease
MeSH terms: Mucocutaneous Lymph Node Syndrome
Intervention: Etanercept; Placebo
Intervention description: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.; Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.
Intervention MeSH terms: Etanercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Approximately 200 subjects will be randomized in a 1:1 ratio to receive Etanercept or Placebo. Subjects are randomized after hospital admission and diagnosis of Kawasaki Disease at eight participating sites. The primary analysis time-point is visit 5 (day 44). Sample size calculation is based on initial IVIG refractory rate at Seattle Children's. Assuming a 17.4% refractory rate in the control group and a 4.3% refractory rate in the Etanercept group, 200 subjects will provide 80% power at a 5% 2-sided type I error rate. Analyses will be based on a modified intention to treat population, including all subjects who were randomized and received at least 1 dose of study drug. Efficacy analyses will be based on randomization assignment, and safety analyses will be based on the treatment actually received. The statistical analysis plan will be finalized prior to database lock and study unblinding.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 205.0
Sex: All
Minimum age: 2 Months
Maximum age: 20 Years
Healthy volunteers: No
Keywords: Etanercept

Summary:

      The purpose of this study is to determine whether Etanercept (Enbrel) when used in
      conjunction with IVIG and aspirin, improves treatment response to IVIG in patients with
      Kawasaki Disease. Funding Source- FDA/OOPD
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male Age 2 months to 20 years of age Female Age 2 months to 11 years of age

          -  Provision of Parental Consent

          -  Kawasaki Disease Presentation

        Exclusion Criteria:

          -  Laboratory Criteria: Any laboratory toxicity, at the time of the screening visit or at
             any time during the study that in the opinion of the Investigator would preclude
             participation in the study or:

               1. Platelet count < 100,000/mm3

               2. WBC count < 3,000 cells/mm3

               3. Hemoglobin, hematocrit, or red blood cell count outside 30% of the upper or lower
                  limits of normal for the Lab

          -  Subject is currently enrolled in another investigational device or drug trial(s), or
             subject has received other investigational agent(s) within 28 days of baseline visit.

          -  Female subjects diagnosed with KD 12 years of age and older.

          -  Subjects who have known hypersensitivity to Enbrel or any of its components or who is
             known to have antibodies to etanercept

          -  Prior or concurrent cyclophosphamide therapy

          -  Prior treatment with any TNF alpha antagonist or steroid within 48 hours prior to
             initiation of IVIG

          -  Concurrent sulfasalazine therapy

          -  Active severe infections within 4 weeks before screening visit, or between the
             screening and baseline visits.

          -  SLE, history of multiple sclerosis, transverse myelitis, optic neuritis, or chronic
             seizure disorder

          -  Known HIV-positive status or known history of any other immuno-suppressing disease.

          -  Any mycobacterial disease or high risk factors for tuberculosis, such as family member
             with TB or taking INH

          -  Untreated Lyme disease

          -  Severe comorbidities (diabetes mellitus requiring insulin, CHF of any severity, MI,
             CVA or TIA within 3 months of screening visit, unstable angina pectoris, uncontrolled
             hypertension (sitting systolic BP > 160 or diastolic BP > 100 mm Hg), oxygen-dependent
             severe pulmonary disease, history of cancer within 5 years [other than resected
             cutaneous basal or squamous cell carcinoma or in situ cervical cancer])

          -  Exposure to hepatitis B or hepatitis C or high risk factors such as intravenous drug
             abuse in patient's mother, or history of jaundice (other than neonatal jaundice). SLE,
             history of multiple sclerosis, transverse myelitis, optic neuritis or chronic seizure
             disorder.

          -  Use of a live vaccine (Measles Mumps Rubella or Varicella) 30 days prior to or during
             this study.

          -  Any condition judged by the patient's physician to cause this clinical trial to be
             detrimental to the patient

          -  History of non-compliance with other therapies

          -  Must not have received immunosuppressive agents for at least three months prior to
             enrollment.