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

Kawasaki Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00841789
• Other study ID #: SEA-12652
• Secondary ID: FD003526
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: August 30, 2018

Study information

• Verified date: April 2023
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: August 30, 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 20 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kawasaki Disease
• Mucocutaneous Lymph Node Syndrome

Intervention

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

Locations

Country	Name	City	State
Canada	Sainte-Justine Hospital	Montreal	Quebec
United States	Montefiore Medical Center	Bronx	New York
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Feinstein Institute for Medical Rsearch	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Michael Portman	Amgen

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Portman MA, Dahdah NS, Slee A, Olson AK, Choueiter NF, Soriano BD, Buddhe S, Altman CA; EATAK Investigators. Etanercept With IVIg for Acute Kawasaki Disease: A Randomized Controlled Trial. Pediatrics. 2019 Jun;143(6):e20183675. doi: 10.1542/peds.2018-3675 — View Citation

Portman MA, Olson A, Soriano B, Dahdah N, Williams R, Kirkpatrick E. Etanercept as adjunctive treatment for acute Kawasaki disease: study design and rationale. Am Heart J. 2011 Mar;161(3):494-9. doi: 10.1016/j.ahj.2010.12.003. — View Citation

Sagiv E, Slee A, Buffone A, Choueiter NF, Dahdah NS, Portman MA. Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial. Cardiol Young. 2022 May 12:1-6. doi: 10.1017/S1047951122001470. Online ahead of print. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Coronary Artery Dimension by z Score Compared With General Estimating Equation	Overall change in coronary z score over time determined using General Estimating Equation in patients from baseline within patients. No change or improved defined by 20% change in z score.; A Z score normalized for body surface area represents how much larger (or smaller) a measured coronary artery internal diameter by echocardiography is compared to the average coronary artery diameter for a child of the same size (body surface area includes both height and weight). There is no minimum or maximum value. Z score above 2.0 is at least 2 standard deviations above mean for population and is considered abnormal. A decrease in z score is favorable.	6 weeks
Other	Overall Change in z Score Over Time in Patients With Dilated Coronary Artery at Baseline Within Patients.	Overall change in z score over time determined using General Estimating Equation in patients with dilated coronary artery at baseline within patients. Overall change in coronary z score over time determined using General Estimating Equation in patients from baseline within patients. A Z score normalized for body surface area represents how much larger (or smaller) a measured coronary artery internal diameter by echocardiography is compared to the average coronary artery diameter for a child of the same size (body surface area includes both height and weight). There is no minimum or maximum value. Z score above 2.0 is at least 2 standard deviations above mean for population and is considered abnormal. A decrease in z score is favorable.	6 weeks
Primary	IVIG Refractory	The primary outcome is the proportion of subjects who become refractory to IVIG. Subjects requiring 1 dose of IVIG are classified as responders and subjects requiring more than 1 dose are classified as IVIG refractory.	42 days after initial dose
Secondary	Determine if Etanercept Treatment Alters the Rate of Coronary Artery Dilation and Disease (CAD) at 2 and 6 Weeks After Treatment in Patients With Dilated Coro	The primary echocardiographic outcome will be the proportion of subjects with improvement defined as (20% change in coronary artery) from the worst findings during the acute study period (scheduled visits from admission to visit 4, including any unscheduled visits) to the primary study outcome time-point at visit 5 (visit 5). This calculation will be based on changes in absolute values and not z-scores as initially planned. Groups will be compared using a logistic model including a binary term for age < versus > 1 year. Two aspects of the echo findings will be considered: Maximum aneurysm size and; Maximum measurements for left main coronary artery (LMCA), left anterior descending artery (LAD) and right coronary artery (RCA).; Change in diameter of each coronary artery will be determined at standard measurement location or aneurysm with the latter taking precedent.	42 days after initial dose