Etanercept in Kawasaki Disease

A Randomized, Double Blind, Placebo Controlled Study of the Effects of Etanercept in Children Presenting With Kawasaki Disease

Sponsors

Lead Sponsor: Michael Portman

Collaborator: Amgen

Source Seattle Children's Hospital
Brief 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

Detailed Description

Kawasaki Disease (KD) is a potentially life threatening acute vasculitis in children with a predilection for involvement of the coronary arteries. Aspirin and Intravenous gamma globulin (IVIG) are principally used for the treatment of the symptoms of Kawasaki Disease. Aspirin reduces inflammation and platelet formation, but has no effect in attenuating the development of coronary abnormalities. Although IVIG reduces inflammation and the prevalence of coronary artery abnormalities, it has a relatively high failure rate of 23-30%, warranting new treatment methods for Kawasaki Disease. We propose a placebo controlled double blinded randomized study to determine if etanercept 0.8 mg/kg subcutaneously (max 25 mg) given three times at weekly intervals starting at initial diagnosis is safe in this patient population and if it is a successful adjunct therapy with IVIG in reducing the incidence of persistent or recurrent fever.

Overall Status Unknown status
Start Date March 2009
Completion Date August 2018
Primary Completion Date January 2018
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Determine if Etanercept at the dosing regimen of 0.8 mg/kg (50 mg max) SQ X3 doses given at weekly intervals, when used in conjunction with IVIG and aspirin will reduce the incidence of fever persistence or recrudescence. 42 days after initial dose
Secondary Outcome
Measure Time Frame
Determine if the safety profile differs between the etanercept treated group and the placebo group. 42 days after initial dose
Determine if Etanercept treatment alters the rate of coronary artery dilation and disease (CAD) at 2 and 6 weeks after treatment. 42 days after initial dose
CRP Laboratory Measurements 42 days after initial dose
Hemoglobin Laboratory Measurements 42 days after initial dose
Enrollment 196
Condition
Intervention

Intervention Type: Drug

Intervention Name: Etanercept

Description: etanercept 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.

Arm Group Label: Arm 1 -Etanercept

Other Name: Enbrel

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo 0.8 mg/kg subcutaneously (max 50 mg) given three times, once a week for three weeks starting at initial diagnosis.

Arm Group Label: 2

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.

Gender: All

Minimum Age: 2 Months

Maximum Age: 20 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Michael A Portman, MD Principal Investigator Seattle Children's Hospital
Location
Facility:
Montefiore Medical Center | Bronx, New York, 10467, United States
Feinstein Institute for Medical Rsearch | New Hyde Park, New York, 11040, United States
Columbia University Medical Center | New York, New York, 10032, United States
Texas Children's Hospital | Houston, Texas, 77030, United States
Primary Children's Medical Center | Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital | Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin | Milwaukee, Wisconsin, 53201, United States
Sainte-Justine Hospital | Montreal, Quebec, H3T 1C5, Canada
Location Countries

Canada

United States

Verification Date

April 2018

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Seattle Children's Hospital

Investigator Full Name: Michael Portman

Investigator Title: Cardiologist

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Arm 1 -Etanercept

Type: Experimental

Description: Drug - Treatment with Etanercept as adjunct to standard treatment with IVIG and aspirin

Label: 2

Type: Placebo Comparator

Description: Placebo

Study Design Info

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.

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov