Wegener's Granulomatosis Clinical Trial
Official title:
A Randomized Trial Examining the Use of Daclizumab in Wegener's Granulomatosis
This study will examine the safety and effectiveness of daclizumab (also called Zenapax or
anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel
inflammation). Wegener's granulomatosis can affect many parts of the body, including the
brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and
other sites. Standard treatment is a combination of prednisone and a cytotoxic agent (a drug
that interferes with cell growth), 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 focus on the effectiveness of
daclizumab in preventing disease relapse.
The Food and Drug Administration approved daclizumab in 1997 for preventing kidney
transplant rejection, and the drug has also been studied in people with an eye infection
called uveitis. The drug works by binding to a protein on T lymphocytes (white blood cells
of the immune system) called CD25. This prevents another protein, called interleukin-2, from
binding to this site, thereby preventing a series of events that normally results in
inflammation.
Patients between 10 and 75 years of age with Wegener's granulomatosis 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 conducted. All patients
will begin treatment with prednisone and cyclophosphamide daily. Those who improve on this
regimen will reduce the prednisone gradually and continue with cyclophosphamide until their
disease is in remission. While taking cyclophosphamide, patients must have blood and urine
tests done every 1 to 2 weeks. Those who achieve disease remission will stop
cyclophosphamide and start taking methotrexate once a week, usually by mouth but possibly by
injection into the muscle or skin. Blood and urine tests will be conducted once a week for 4
weeks while the dosage is being adjusted and then once a month for the duration of
treatment. Patients on methotrexate whose prednisone dose is reduced to 10 to 30 mg every
other day will be randomly assigned either to receive or not receive daclizumab in addition
to the methotrexate. Daclizumab is given intravenously (through a plastic tube inserted into
a vein) the day after the randomization, then again in 2 weeks, 4 weeks, and once a month
for 18 months.
All patients will continue to taper their prednisone dose until it is stopped. Methotrexate
will continue for 2 years. Patients whose disease remains in remission at this time will
decrease the methotrexate dose. If there is no active disease when both prednisone and
methotrexate have been stopped, no further treatment will be given. If disease recurs at a
later time, treatment will be reinstituted. The treatment will be determined by the severity
of disease, other medical conditions, and history of side effects. Patients not randomized
to daclizumab who relapse while still taking methotrexate may be offered re-treatment with
daclizumab.
Patients will be evaluated in the outpatient clinic every 4 to 8 weeks until randomization.
Patients not taking daclizumab will be followed every 4 to 12 weeks; those taking the drug
will be seen every 2 weeks for the first month, every month after that during the 18-month
treatment period, and every 4 to 12 weeks until all medications stop. Follow-up evaluations
include a physical examination, blood draws and, if medically indicated, X-rays. The total
study duration is 60 to 70 months.
The purpose of this study is to assess the safety and efficacy of daclizumab as an adjunctive treatment to methotrexate in maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will receive methotrexate for remission maintenance. Following the switch to methotrexate and when the prednisone dose has been tapered to 20mg QOD (plus or minus 10mg QOD), patients in remission will be randomized to receive daclizumab or not receive daclizumab. Those randomized to receive daclizumab will be treated with 1 mg/kg intravenously on day 0, week 2, week 4 and every month thereafter for a total of 18 months (20 doses). Regardless to which arm the patient is randomized, they will continue to receive methotrexate. Two years after the methotrexate was started, if the patient remains in remission, this will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events. ;
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
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