This study will examine the use of etanercept (also called Enbrel or TNFR:Fc) in patients
with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's
granulomatosis may affect many parts of the body, including the brain, nerves, eyes, sinuses,
lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Generally, the
greater the disease involvement, the more life-threatening it is. Standard treatment is a
combination of prednisone and a cytotoxic agent-usually cyclophosphamide or methotrexate.
However, many patients treated with this regimen have a disease relapse, and others cannot
take these drugs because of severe side effects. This study will evaluate etanercept's safety
and effectiveness, and particularly its value in reducing the need for prednisone and
preventing disease relapse.
The Food and Drug Administration has approved etanercept for treating rheumatoid arthritis,
another inflammatory disease. The drug works by blocking the activity of TNF-a protein made
by white blood cells that is involved in the inflammatory process. Since prednisone also
affects inflammatory proteins and lowers TNF production, the use of etanercept may reduce the
need for prednisone in patients with Wegener's granulomatosis, and thus the risk of its side
effects.
Patients between 10 and 70 years of age with Wegener's granulomatosis who have never taken
prednisone, methotrexate or cyclophosphamide, or have taken these drugs for less than 3 weeks
may be eligible for this study.
Participants will have a medical history review and physical examination, including
laboratory studies. If medically indicated, X-rays, consultations and biopsies (surgical
removal of a small tissue sample) of affected organs will also be done. All patients will
begin treatment with prednisone, methotrexate and etanercept. Those who improve on this
regimen will stop prednisone gradually over 3 months. Those who achieve disease remission at
the end of another 3 months will be randomly assigned to either continue taking etanercept
and methotrexate for another 12 months or to stop etanercept and continue only methotrexate
for the next 12 months (after which methotrexate will gradually be stopped). Patients who are
not in remission by the 6-month point will continue taking etanercept until they go into
remission, when they will be assigned to stop or not stop etanercept, as described above.
Patients who do not achieve remission within 12 months of beginning treatment will be taken
off the study. Patients who have a disease relapse while on the study will likely be switched
to treatment with prednisone and either methotrexate or cyclophosphamide. Patients randomized
to stop etanercept and who have a relapse within a year of stopping the drug may be offered
re-treatment on this protocol, but with continuing etanercept for a full year after
remission.
Patients will be evaluated in the outpatient clinic every 2 to 4 weeks for the first 4 months
and every 1 to 3 months after that. Patients whose disease is in remission and who stop all
medications will be followed every 3 to 6 months for 2 years. Follow-up evaluations include a
physical examination, blood draws and, if medically indicated, X-rays. The total study
duration is 60 to 70 months.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)