Patients with a diagnosis of EGPA with newly-diagnosed disease or with a relapsing disease at the time of screening MedDRA version: 19.0 Level: PT Classification code 10048594 Term: Allergic granulomatous angiitis System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: RITUXIMAB
Product Name: RITUXIMAB
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
Other descriptive name: RITUXIMAB
Concentration unit: g gram(s)
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion 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) > ou=3, - Patients within the first 21 days following initiation/increase of corticosteroids at a dose =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 all duration of the study, - 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 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 or cyclophosphamide,(only patients DFS< ou=1) - 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 < ou=4,000/mm3, - Patients who have platelet count < ou =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. -
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The percentage of patients who obtained a BVAS=0 at day 180. Remission will be defined as the absence of disease activity attributable to EGPA vasculitis manifestations (parenchymal lung disease, peripheral nerve involvement, skin, cardiac, renal and/or gastrointestinal signs), corresponding to BVAS=0, with a prednisone dose < ou =7.5 mg/day. Secondary assessment criteria - The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at days 180 and 360 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorraghic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions - The area under the curve for corticosteroids at at days 180 and 360 day 180 and day 360 in the two treatment groups - The Vasculitis Damage Index at days 180 and 360 at day 180 and day 360 in the two treatment groups - The HAQ and SF-36 at days 180 and 360 at day 180 and day 360 in the two treatment groups - Evolution of ANCA titers and CD19+ cells in the two treatment groups, and correlation with clinical events ;Main Objective: To determine the efficacy of rituximab and glucocorticoids to induce a complete remission, defined as a Birminghman Vasculitis Activity Score (BVAS) of 0 and a prednisone dose < ou =7.5 mg/day at day 180, in patients with newly-diagnosed or relapsing EGPA.;Secondary Objective: - To compare the safety profile of rituximab and conventional treatment at days 180 and 360 - To measure the corticosteroid dose at days 180 and 360 and to compare the corticosteroid sparing effect of rituximab versus conventional therapy - To compare sequelae assessed by the Vasculitis Damage Index at days 180 and 360 in both a | — |
Countries
France
Contacts
Public ContactDRCD Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed