The sample size is 180 patients, to be recruited from 8 clinical centers in the United States over a 30-month period. Patients are assigned randomly to receive either etanercept or placebo in an allocation ratio of 1:1. Randomization is stratified by clinic and disease severity (limited versus severe). Every patient enrolled will have a Birmingham Vasculitis Activity Score for WG (BVAS/WG) of at least 3, ensuring unequivocally active disease.

In addition to either etanercept or placebo, all patients receive standard treatment for WG depending on severity of the disease. Those with limited WG receive methotrexate and corticosteroids, and those with severe WG receive cyclophosphamide and corticosteroids. After the patients’ disease is controlled with therapy (i.e., the standard treatment plus either etanercept or placebo), the standard medications are tapered according to regimens designed to ensure patient safety, diminish morbidity associated with the standard medications, and test the efficacy of etanercept in sustaining disease remissions.

Followup evaluations will be conducted at 6 weeks and 3 months after randomization, and every 3 months thereafter. All randomized patients, regardless of whether or not they remain on their assigned treatments, will be followed until the common closing date of the trial, defined as 12 months after enrollment of the last patient.