Wegener's Granulomatosis Etanercept Trial (WGET)
11 Years
N/A
Both
Wegener's Granulomatosis
Trial Information
Wegener's Granulomatosis Etanercept Trial (WGET)
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.
Inclusion Criteria:
- Minimum weight of 40 kg.
- Diagnosis of WG, excluding infections, malignancies, systemic autoimmune disorders,
and other forms of vasculitis that may mimic WG.
- At least two of the five modified American College of Rheumatology (ACR) criteria for
a diagnosis of WG. The modified ACR criteria are: (1) nasal or oral inflammation,
defined as the development of painful or painless oral ulcers or purulent or bloody
nasal discharge; (2) abnormal chest radiograph, defined as the presence of nodules,
fixed infiltrates, or cavities; (3) active urinary sediment, defined as microscopic
hematuria (> 5 red blood cells per high-power field) or red blood cell casts; (4)
granulomatous inflammation on biopsy, defined as histologic changes showing
granulomatous inflammation within the wall of an artery or in the perivascular or
extravascular area (artery or arteriole); and (5) positive serum ELISA for ANCAs
(anti-neutrophil cytoplasmic antibodies) directed at PR-3.
- Birmingham Vasculitis Activity Score (BVAS) score 3 or greater within 28 days of
randomization. This may include either the presence of one or more major items (3
points each) or the presence of three or more minor items (1 point each).
- Willingness and ability, with the assistance of a caregiver if necessary, to comply
with treatment and followup procedures.
- Willingness of men and women of childbearing potential to practice an adequate method
of birth control during the study and for 3 months afterwards.
- Willingness to limit alcohol consumption to one alcoholic drink per week while taking
methotrexate.
- Willingness to refrain from breast-feeding during the study and for 3 months
afterwards.
- Collection of all baseline data within 14 days prior to randomization.
- Signed consent statement.
Exclusion Criteria:
- Presence of an active systemic infection.
- White blood cell count less than 4,000/mm cubed or a platelet count less than
120,000/mm cubed.
- Creatinine greater than 2.0 mg/dL secondary to non-WG causes (e.g., hypertensive
nephropathy) for a patient with limited disease.
- Known acute or chronic liver disease.
- History of multiple sclerosis or other neurological symptoms suggesting a
demyelinating syndrome.
- Current evidence of malignancy or malignancy diagnosed within 5 years of study entry.
Patients with squamous or basal cell carcinomas of the skin may be enrolled if they
have received curative surgical treatment.
- Positive serum pregnancy test for women of childbearing potential.
- Previous treatment with specific therapies directed against tumor necrosis factor,
e.g., etanercept or infliximab.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Outcome Measure:
Number of patients in the two treatment arms who achieve sustained remissions as measured by the Birmingham Vasculitis Activity Score (BVAS) for WG
Outcome Time Frame:
Measured at study completion
Principal Investigator
John H. Stone, MD, MPH
Investigator Role:
Principal Investigator
Investigator Affiliation:
Johns Hopkins University
Authority:
United States: Food and Drug Administration
Study ID:
N01 AR92240
NCT ID:
NCT00005007
Start Date:
June 2000
Completion Date:
March 2003
Related Keywords:
- Wegener's Granulomatosis
- Wegener's granulomatosis
- Vasculitis
- Etanercept
- Tumor necrosis factor
- Wegener Granulomatosis
Name | Location |
|---|---|
| Johns Hopkins University | Baltimore, Maryland 21205 |
| University of Michigan | Ann Arbor, Michigan 48109-0624 |
| Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
| Mayo Clinic | Rochester, Minnesota 55905 |
| Beth Israel Medical Center | New York, New York 10003 |
| University of California, San Francisco | San Francisco, California 94143 |
| Boston University | Boston, Massachusetts 02118 |
| Duke University | Durham, North Carolina 27710 |
