Clinical trial NCT00104299
Conditions: Vasculitis Wegener's Granulomatosis Microscopic Polyangiitis
Keywords: ANCA Vasculitis Wegener's Granulomatosis microscopic polyangiitis ANCA-positive ANCA-associated ANCA-associated vasculitis MPA
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2005-01-01; Completion date: 2010-01-01
Enrollment: 197 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common type of small blood vessel inflammation in adults. ANCA-associated vasculitis includes Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Rituximab is a man-made antibody used to treat certain types of cancer. The purpose of this study is to determine the effectiveness of rituximab in treating patients with WG and MPA.

Study hypothesis: Rituximab is not inferior to conventional therapy in its ability to induce disease remission by Month 6.

Detailed description:
Current conventional therapies for ANCA-associated vasculitis (AAV) are associated with high incidences of treatment failure, disease relapse, substantial toxicity, and patient morbidity and mortality. Rituximab is a monoclonal antibody used to treat non-Hodgkin's lymphoma. This study will evaluate the efficacy of rituximab with glucocorticoids in inducing disease remission in patients with severe forms of AAV (WG and MPA).

The study consists of two phases: a 6-month remission induction phase, followed by a 12-month remission maintenance phase. All participants will receive at least 1 g of pulse intravenous methylprednisolone or a dose-equivalent of another glucocorticoid preparation. Depending on the participant's condition, he or she may receive up to 3 days of intravenous methylprednisolone for a total of 3 g of methylprednisolone (or a dose-equivalent). During the remission induction phase, all participants will receive oral prednisone daily (1 mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6 study visit.

Next, participants will be randomly assigned to one of two arms. Arm 1 participants will receive rituximab (375 mg/m\^2) infusions once weekly for 4 weeks and cyclophosphamide (CYC) placebo daily for 3 to 6 months. Arm 2 participants will receive rituximab placebo infusions once weekly for 4 weeks and CYC daily for 3 to 6 months. During the remission maintenance phase, participants in Arm 1 will discontinue CYC placebo and start oral azathioprine (AZA) placebo daily until Month 18. Participants in Arm 2 will discontinue CYC and start AZA daily until Month 18. Participants who fail treatment before Month 6 will be crossed over to the other treatment arm unless there are specific contraindications. Participants in either group who reach clinical remission before they complete 6 months of therapy may switch from CYC/placebo to AZA/placebo if directed by their physicians.

All participants will be followed for at least 18 months. Initially, study visits are weekly, progressing to monthly and then quarterly visits as the study proceeds. Blood collection will occur at each study visit.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Rituximab plus cyclophosphamide placebo (rituximab group) intervention 2: Cyclophosphamide plus rituximab placebo (control group) intervention 3: Azathioprine intervention 4: Methylprednisolone (or other glucocorticoid) intervention 5: Prednisone
Intervention descriptions: intervention 1: 375 mg/m\^2 infusions once weekly for 4 week intervention 2: 2 mg/kg/day orally for months 1-3 intervention 3: 2 mg/kg/day orally for months 4-6 intervention 4: 1 g/day intravenously for up to 3 days within 14 days prior to receiving rituximab intervention 5: During the remission induction phase, all participants will receive oral prednisone daily (1 mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6 study visit.

Protocol documents: