Rituximab in Eosinophilic Granulomatosis With Polyangiitis (REOVAS)
Eosinophilic Granulomatosis With Polyangiitis (EGPA)
About this trial
This is an interventional treatment trial for Eosinophilic Granulomatosis With Polyangiitis (EGPA) focused on measuring Rituximab, remission induction, eosinophilic granulomatosis with polyangiitis
Eligibility Criteria
Inclusion Criteria:
- Patients with a diagnosis of EGPA independently of ANCA status,
- Patient aged of 18 years or older,
- Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥3,
- Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤ 1 mg/kg/day (pulses of methylprednisolone before oral corticosteroid therapy are authorized) ,
- Patient able to give written informed consent prior to participation in the study.
Exclusion Criteria:
- Patients with GPA, MPA, or other vasculitides, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
- Patients with vasculitis in remission of the disease defined as a BVAS <3,
- Patients with severe cardiac failure defined as class IV in New York Heart Assocation
- Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
- Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
- Pregnant women and lactation. Patients with childbearing potential should have reliable contraception for the 12 months duration of the study,
- Patients with EGPA who have already been treated with rituximab within the previous 12 months,
- Patients with hypersensitivity to a monoclonal antibody or biologic agent,
- Patients with contraindication to use rituximab, cyclophosphamide, mesna or azathioprine,
- Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
- Patients included in other investigational therapeutic study within the previous 3 months,
- Patients suspected not to be observant to the proposed treatments,
- Patients who have white blood cell count ≤4,000/mm3,
- Patients who have platelet count ≤100,000/mm3,
- Patients who have ALT or AST level greater that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease,
- Patients unable to give written informed consent prior to participation in the study.
Sites / Locations
- Hôpital Cochin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Placebo Comparator
Experimental
Active Comparator
Rituximab with FFS=0
Conventional therapy with FFS=0
Rituximab with FFS≥1
Conventional therapy with FFS≥1
All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group. Patients with FFS=0 will receive 1 gram of rituximab at day 1 and day 15 as induction treatment
All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group. Patients with FFS=0 will receive placebo-rituximab at day 1 and day 15.
All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group. Patients with FFS≥1 will receive a total of 9 pulses : 1 gram of rituximab at day 1 and day 15 as induction treatment placebo-cyclophosphamide at days 1, 15, 29, 50, 71, 92, 113, 134 and 155. Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.
All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group. Patients with FFS≥1 will receive intravenous pulses of cyclophosphamide for a total of 9 pulses: 600 mg/m2 at days 1, 15 and 29, and then 500 mg-fixed dose at days 50, 71, 92, 113, 134 and 155. Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.