Patients with newly diagnosed or relapsing MPA, without any poor prognosis marker (FFS=0). Stratification will be made according to peripheral nerve involvement. MedDRA version: 20.0 Level: PT Classification code 10063344 Term: Microscopic polyangiitis System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: RIXATHON 500mg
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient (male or female) aged 18 years old and over 2. Patient agreement to participate in the study and signed written informed consent 3. Patient with MPA according to the CHCC established in 2012 4. Absence of any poor prognosis factor (modified five factor score (FFS) 1996=0) 5. Patient with recent onset or relapse of the disease (=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1. Small-sized vessels vasculitis not associated with anti-MPO antibody or associated with anti-PR3 positivity. 2. Patients with either GPA or EGPA vasculitis according to ACR criteria. 3. Patient with a modified FFS 1996 = 1. 4. Patient with alveolar haemorrhage requiring mechanical ventilation. 5. Patient with previous glucocorticoids treatment >1 month and >10mg/day either for vasculitis or for any other reason. 6. Patient already receiving immunosuppressant or biological agent. Prior treatment with any of the following: - azathioprine, methotrexate, mycophenolate mophetil, mycophenolic acid within 4 weeks before inclusion - alkylant agent such as cyclophosphamide within 6 months before inclusion - anti-TNF? inhibitors : infliximab within 8 weeks, adalimumab and etanercept within 2 weeks before inclusion -anti-CD20 therapy within one year before inclusion. 7. Patient with a previous diagnosis of cancer < 5 years (except for in situ cervical cancer and skin carcinoma with R0 resection) 8. Patient with acute infections or chronic active infections (including HIV, hepatitis B or C). 9. Breast feeding woman or woman refusing the use of a contraceptive method for the 18 months’ duration of the study. 10. Contraindication to treatment (glucocorticoids or rituximab). 11. Unable to receive written informed consent of patient. Patient unable to understand the protocol. 12. Patient already in another therapeutic protocol. 13. Patient without social security. 14. Patient with severe cardiac failure defined as class IV according to New York Heart Association classification. 15. Patients with hypersensitivity to a monoclonal antibody or biological agent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To demonstrate the superiority of a rituximab-based treatment compared to standard therapy in patients with microscopic polyangiitis without any bad prognosis marker.;Secondary Objective: 1. Demonstrate a glucocorticoids sparing effect of the rituximab-based regimen by measuring the cumulative dose of glucocorticoids in each group from M0 to M18. 2. Compare the number of patients who achieve a complete remission. Remission is defined by the absence of sign attributable to vasculitis and a BVAS=0 at M3 3. Among patients who enter remission, compare proportion of patients who relapse and time to first relapse. 4. Compare proportion of major and minor relapses between arms. 5. Compare overall survival rate in each arm at M18 6. Compare the quality of life and handicap of patients and compare between groups. Quality of life and handicap is evaluated with scores HAQ, SF36 and EQ-5D 7. Compare the sequelae of patients at the end of follow-up with the Vasculitis Damage Index (VDI) 8. Compare the proportion of patients who are still on glucocorticoids for their vasculitis at the end of the follow-up (M18) 9. Evaluate the number and severity of side effect. ;Primary end point(s): Assessment criterion: Disease free survival from month 3 to month 18 in patients with microscopic polyangiitis treated with rituximab and glucocorticoids compared to glucocorticoids alone. Primary failure: Vasculitis requiring a modification of immunosuppressive treatment or prednisone tapering protocol before M3 Remission is defined by the absence of sign attributable to vasculitis and a Birmingham Vasculitis Activity Score (BVAS)=0 at M3 Relapse is defined after visit M3 by a BVAS>0 or the impossibility to decrease glucocorticoids according to the predefined protocol. Therefore, patients who experience a primary failure or fail to enter remission or relapse will be considered as treatment failure.;Timepoint(s) of evaluation of this end point: Month 3 to month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Demonstrate a glucocorticoids sparing effect of the rituximab-based regimen by measuring the cumulative dose of glucocorticoids in each group from M0 to M18. GC dose will be recorded at each visit 2. Compare the number of patients who achieve a complete remission. Remission is defined by the absence of sign attributable to vasculitis and a BVAS=0 at M3 3. Among patients who enter remission, compare proportion of patients who relapse and time to first relapse. Relapse is defined after visit M3 by the reoccurrence of signs or symptoms attributable to vasculitis and a BVAS=1 or the impossibility to decrease GC therapy according to the predefined protocol 4. Compare proportion of major and minor relapses between arms. Major relapse is defined by reappearance or worsening of disease with a BVAS=1 and involvement of at least one major organ, a life-threatening manifestation, or both Minor relapse is defined by reappearance or worsening of disease with a BVAS=1, not corresponding to a major relapse 5. Compare overall survival rate in each arm at M18 6. Compare the quality of life and handicap of patients and compare between groups. Quality of life and handicap is evaluated with scores HAQ, SF36 and EQ-5D 7. Compare the sequelae of patients at the end of follow-up with the Vasculitis Damage Index (VDI) 8. Compare the proportion of patients who are still on glucocorticoids for their vasculitis at the end of the follow-up (M18) 9. Evaluate the number and severity of side effect. Record of adverse events and serious adverse events related to vasculitis or treatment in each group at each visit. Classification is made according to the CTCAE toxicity grading scale.;Timepoint(s) of evaluation of this end point: At each visit from M0 to M18 | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Outcome results
None listed