Etanercept for Wegener's Granulomatosis

NCT00005007 | Completed Phase 2

• 2 other identifiers: N01 AR92240NIAMS-041
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 8

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.

Conditions

Wegener's Granulomatosis

Keywords

Wegener's granulomatosis; Vasculitis; Etanercept; Tumor necrosis factor

Outcome Measures

Primary Outcomes (1)

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

  Measured at study completion

Interventions

Etanercept DRUG

Eligibility Criteria

• Age: 11 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (8)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Beth Israel Medical Center

New York, New York, 10128, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (10)

• Stone JH, Uhlfelder ML, Hellmann DB, Crook S, Bedocs NM, Hoffman GS. Etanercept combined with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum. 2001 May;44(5):1149-54. doi: 10.1002/1529-0131(200105)44:53.0.CO;2-F.

  PMID: 11352248 BACKGROUND

• Stone JH, Hoffman GS, Merkel PA, Min YI, Uhlfelder ML, Hellmann DB, Specks U, Allen NB, Davis JC, Spiera RF, Calabrese LH, Wigley FM, Maiden N, Valente RM, Niles JL, Fye KH, McCune JW, St Clair EW, Luqmani RA; International Network for the Study of the Systemic Vasculitides (INSSYS). A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum. 2001 Apr;44(4):912-20. doi: 10.1002/1529-0131(200104)44:43.0.CO;2-5.

  PMID: 11318006 BACKGROUND

• WGET Research Group. Design of the Wegener's Granulomatosis Etanercept Trial (WGET). Control Clin Trials. 2002 Aug;23(4):450-68. doi: 10.1016/s0197-2456(02)00209-x.

  PMID: 12161090 BACKGROUND

• Stone JH; Wegener's Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial. Arthritis Rheum. 2003 Aug;48(8):2299-309. doi: 10.1002/art.11075.

  PMID: 12905485 RESULT

• Merkel PA, Lo GH, Holbrook JT, Tibbs AK, Allen NB, Davis JC Jr, Hoffman GS, McCune WJ, St Clair EW, Specks U, Spiera R, Petri M, Stone JH; Wegener's Granulomatosis Etanercept Trial Research Group. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med. 2005 Apr 19;142(8):620-6. doi: 10.7326/0003-4819-142-8-200505030-00011.

  PMID: 15838068 RESULT

• Stone JH, Rajapakse VN, Hoffman GS, Specks U, Merkel PA, Spiera RF, Davis JC, St Clair EW, McCune J, Ross S, Hitt BA, Veenstra TD, Conrads TP, Liotta LA, Petricoin EF 3rd; Wegener's Granulomatosis Etanercept Trial Research Group. A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis. Arthritis Rheum. 2005 Mar;52(3):902-10. doi: 10.1002/art.20938.

  PMID: 15751091 RESULT

• Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, Davis JC, Ytterberg SR, St Clair EW, McCune WJ, Specks U, Allen NB, Luqmani RA, Stone JH; WGET Research Group. Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum. 2005 Jul;52(7):2168-78. doi: 10.1002/art.21117.

  PMID: 15986348 RESULT

• Wung PK, Holbrook JT, Hoffman GS, Tibbs AK, Specks U, Min YI, Merkel PA, Spiera R, Davis JC, St Clair EW, McCune J, Ytterberg SR, Allen NB, Stone JH; WGET Research Group. Herpes zoster in immunocompromised patients: incidence, timing, and risk factors. Am J Med. 2005 Dec;118(12):1416. doi: 10.1016/j.amjmed.2005.06.012.

  PMID: 16378799 RESULT

• Stone JH, Holbrook JT, Marriott MA, Tibbs AK, Sejismundo LP, Min YI, Specks U, Merkel PA, Spiera R, Davis JC, St Clair EW, McCune WJ, Ytterberg SR, Allen NB, Hoffman GS; Wegener's Granulomatosis Etanercept Trial Research Group. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum. 2006 May;54(5):1608-18. doi: 10.1002/art.21869.

  PMID: 16646004 RESULT

• Clowse ME, Copland SC, Hsieh TC, Chow SC, Hoffman GS, Merkel PA, Spiera RF, Davis JC Jr, McCune WJ, Ytterberg SR, St Clair EW, Allen NB, Specks U, Stone JH; WGET Research Group. Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's). Arthritis Care Res (Hoboken). 2011 Dec;63(12):1777-81. doi: 10.1002/acr.20605.

  PMID: 22127969 DERIVED

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Vasculitis

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• John H. Stone, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 24, 2000
• First Posted: March 27, 2000
• Study Start: June 1, 2000
• Primary Completion: March 1, 2003
• Study Completion: March 1, 2003
• Last Updated: December 28, 2007

Record last verified: 2007-12

Locations

US (8)