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

NCT00841789 | Completed Phase 2 Results DMC

• 2 other identifiers: SEA-12652FD003526
• Study Type: interventional
• Target: 205
• Locations: 2 countries
• Sites: 8

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

Conditions

Mucocutaneous Lymph Node Syndrome; Kawasaki Disease

Keywords

Etanercept

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

  42 days after initial dose

Other Outcomes (2)

• Change in Coronary Artery Dimension by z Score Compared With General Estimating Equation

  6 weeks

• Overall Change in z Score Over Time in Patients With Dilated Coronary Artery at Baseline Within Patients.

  6 weeks

Study Arms (2)

Arm 1 -Etanercept

EXPERIMENTAL

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

Drug: Etanercept

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Etanercept DRUG

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

Also known as: Enbrel

Arm 1 -Etanercept

Placebo DRUG

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

2

Eligibility Criteria

• Age: 2 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Platelet count \< 100,000/mm3
• WBC count \< 3,000 cells/mm3
• 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

Sponsors & Collaborators

• Michael Portman: lead
• Amgen: collaborator

Study Sites (8)

Feinstein Institute for Medical Rsearch

New Hyde Park, New York, 11040, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53201, United States

Location

Sainte-Justine Hospital

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (3)

• 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.

  PMID: 21392603 BACKGROUND

• 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. Epub 2019 May 2.

  PMID: 31048415 RESULT

• 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. 2023 Apr;33(4):613-618. doi: 10.1017/S1047951122001470. Epub 2022 May 12.

  PMID: 35545881 RESULT

MeSH Terms

Conditions

Mucocutaneous Lymph Node Syndrome

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Michael A Portman
• Organization: Seattle Childrens hospital

michael.portman@seattlechildrens.org

2069871014

Study Officials

• Michael A Portman, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Cardiologist

Model Details: 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.

Study Record Dates

• First Submitted: February 10, 2009
• First Posted: February 11, 2009
• Study Start: March 1, 2009
• Primary Completion: January 1, 2018
• Study Completion: August 30, 2018
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-04

Locations

US (7); CA (1)