Etanercept for Wegener’s Granulomatosis

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Brief Title

Etanercept for Wegener's Granulomatosis

Official Title

Wegener's Granulomatosis Etanercept Trial (WGET)

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.
    

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.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Number of patients in the two treatment arms who achieve sustained remissions as measured by the Birmingham Vasculitis Activity Score (BVAS) for WG


Condition

Wegener's Granulomatosis

Intervention

Etanercept


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

181

Start Date

June 2000

Completion Date

March 2003

Primary Completion Date

March 2003

Eligibility 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.
      

Gender

All

Ages

11 Years - N/A

Accepts Healthy Volunteers

No

Contacts

John H. Stone, MD, MPH, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00005007

Organization ID

N01 AR92240

Secondary IDs

NIAMS-041


Study Sponsor

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborators

 FDA Office of Orphan Products Development

Study Sponsor

John H. Stone, MD, MPH, Principal Investigator, Johns Hopkins University


Verification Date

December 2007