Granulomatosis With Polyangiitis (Wegener'
Conditions
Interventions
Experimental: Rituximab Maintenance. Rituximab maintenance: 1g at 4, 8, 12, 16 &
20 months with standardised steroid taper.
Active Comparator: Azathioprine Maintenance. Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation). Azathiopr
Sponsors
University of Miyazaki Hospital
The European Vasculitis Society Vasculitis Clinical Research Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants must meet all of the following criteria to be eligible for enrolment: 1). Written informed consent 2). A diagnosis of AAV (granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis), according to the definitions of the Chapel Hill Consensus Conference 3). Current or historical ANCA positivity either by ELISA or immunofluorescence. 4). Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegener's (BVAS/WG), in patients that have previously achieved remission following induction therapy All patients will receive induction therapy with rituximab. Only those entering remission by 4 months will be randomised 1:1 to the rituximab or control groups.
Exclusion criteria
Exclusion criteria: 1). Age < 18 years. 2). Previous therapy with: a). Any biological B cell depleting agent within the past 6 months b). Alemtuzumab or anti-thymocyte globulin within the last 12 months; c). IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months; d). Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer). 3). Exclusions related to general health: a). Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation; b). Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis; c). Any concomitant condition anticipated to likely require greater than 4 weeks per year of oral or systemic glucocorticoid use and which would preclude compliance with the glucocorticoid protocol (e.g. poorly-controlled asthma, COPD, psoriasis, or inflammatory bowel disease); d). History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies; e). Known infection with HIV, a past or current history of hepatitis B virus or hepatitis C virus infection; f). Ongoing or recent (last 12 months) evidence of active tuberculosis or known active infection or evidence of untreated latent tuberculosis. Screening for tuberculosis is as per local practice; g). History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure; h). Pregnancy or inadequate contraception in pre-menopausal women; i). Breast feeding or lactating. 4. Exclusion criteria related to laboratory parameters: a). Bone marrow suppression; b). Elevation of Aspartate aminotransferase or alanine aminotransferase or amylase
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to disease relapse (either minor or major relapse) from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients who maintain remission at 24 and 48 months 2. Time to a major or second minor relapse 3. Cumulative accrual of damage as measured by the combined damage assessment score (CDA) 4. Health-related quality of life as measured using SF-36 5. Cumulative glucocorticoid exposure 6. Severe adverse event rate 7. Infection rate | — |
Countries
Japan,North America,South America,Australia,Europe
Contacts
Public ContactToshiko Ito-Ihara
Kyoto University Hospital Institute for Advancement of Clinical and Translational Science
Outcome results
None listed