Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis (ITN021AI)
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
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
A Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) score of 0 with prednisone taper successfully completed at six months. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease.
6 months post-randomization
John H. Stone, MD, MPH
Johns Hopkins University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Alabama||Birmingham, Alabama|
|Boston University||Boston, Massachusetts 02118|
|Duke University||Durham, North Carolina 27710|
|Hospital for Special Surgery||New York, New York 10021|
|The Cleveland Clinic||Cleveland, Ohio 44195|
|Mayo Clinic Foundation||Rochester, Minnesota 55905|