Etanercept for Wegener's Granulomatosis

Overview

This study will determine if the drug etanercept, also called Enbrel, is effective in producing and maintaining remission (reduction of disease symptoms) of Wegener's granulomatosis (WG). Etanercept blocks the action of tumor necrosis factor-alpha, a substance that may be involved in inflammatory conditions such as WG. Eight clinical centers around the United States will enroll 181 people who have WG. Patients will have an equal chance to receive either etanercept or placebo (inactive treatment). We will treat patients with standard medications for WG in addition to either etanercept or placebo. We will treat all patients with tapering doses of corticosteroids. After the patients' disease is controlled (in remission), we will reduce the dosages of the standard medications to lower the risk of side effects associated with these drugs. During the study, we will collect and save blood and tissues samples from patients and use the samples to address other medical questions, such as the cause of WG and factors that lead to disease progression.

The Wegener's Granulomatosis Etanercept Trial (WGET) is a randomized, placebo-controlled clinical trial. A primary objective of the trial is to evaluate the safety and efficacy of etanercept (Enbrel; Immunex Corporation, Seattle, WA) for the induction and maintenance of disease remissions for people with Wegener's granulomatosis (WG) when used in conjunction with standard medications. A secondary objective is to develop a specimen bank of serum, plasma, whole blood, and tissue biopsy samples that may be used to address basic questions regarding the etiology, pathophysiology, and monitoring of WG. The trial is a phase II/III randomized, double-masked, multicenter trial with a parallel treatment design. We will assign patients randomly to either etanercept or placebo in an assignment ratio of 1:1. In addition to either etanercept or placebo, we will treat all patients with standard drug regimens for WG according to the severity of their disease. We will treat those with limited WG with methotrexate and corticosteroids, and those with severe WG with cyclophosphamide and corticosteroids. After the patients' disease is controlled with therapy (i.e., the standard treatment regimen plus either etanercept or placebo), we will taper the standard medications 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. The principal outcome measure in this trial is the number of patients in the two treatment arms who achieve sustained remissions measured by the Birmingham Vasculitis Activity Score for WG (BVAS). The sample size is 181 patients recruited at eight clinical centers in the United States. We will stratify randomization by clinic and disease severity (limited versus severe). Every patient enrolled will have a BVAS of at least three, insuring unequivocally active disease. We will follow all randomized patients, regardless of whether or not they remain on their assigned treatments, until the common closing date of the trial, defined as 12 months after enrollment of the last patient. We will perform the primary analyses on an intention-to-treat basis.