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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)