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Etanercept for Wegener's Granulomatosis

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ClinicalTrials.gov Identifier: NCT00005007
Recruitment Status : Completed
First Posted : March 27, 2000
Last Update Posted : December 28, 2007
FDA Office of Orphan Products Development
Information provided by:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Wegener's Granulomatosis Drug: Etanercept Phase 2 Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Wegener's Granulomatosis Etanercept Trial (WGET)
Study Start Date : June 2000
Actual Primary Completion Date : March 2003
Actual Study Completion Date : March 2003

Primary Outcome Measures :
  1. Number of patients in the two treatment arms who achieve sustained remissions as measured by the Birmingham Vasculitis Activity Score (BVAS) for WG [ Time Frame: Measured at study completion ]

Information from the National Library of Medicine

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Ages Eligible for Study:   11 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005007

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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10128
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
FDA Office of Orphan Products Development
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Principal Investigator: John H. Stone, MD, MPH Johns Hopkins University
Publications of Results:

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: John H. Stone, M.D., M.P.H., Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00005007    
Other Study ID Numbers: N01 AR92240
First Posted: March 27, 2000    Key Record Dates
Last Update Posted: December 28, 2007
Last Verified: December 2007
Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Wegener's granulomatosis
Tumor necrosis factor
Additional relevant MeSH terms:
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Granulomatosis with Polyangiitis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vascular Diseases
Cardiovascular Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors