Etanercept for Wegener's Granulomatosis

• Status: Completed
• Trial end date: 2003-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Collaborator: FDA Office of Orphan Products Development
• Treatments: Etanercept

Criteria

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.