Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis (RITUXGOPRO)

Assistance Publique - Hôpitaux de Paris

Status and phase: Active, not recruiting; Phase 3

Conditions: Microscopic Polyangiitis (MPA)

Treatments: Drug: placebo; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT03920722

P170909J

2018-000637-12 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to determine wether a rituximab-based treatment compared to standard therapy (glucocorticoid alone) in patients with microscopic polyangiitis without any bad prognosis marker increases the remission and reduces the relapse free survival rate.

Full description

Microscopic polyangiitis (MPA), is a small-sized vessel necrotizing vasculitis associated with anti-neutrophils cytoplasmic antibody (ANCA). Treatment of ANCA associated vasculitis (AAV) was previously based on glucocorticoids (GC) and cyclophosphamide. It has been demonstrated in two prospective randomized trials that rituximab is as effective as cyclophosphamide in the induction treatment of GPA and severe MPA. In addition, it was shown in GPA and MPA that rituximab is superior to azathioprine as maintenance therapy.

Patients with MPA without poor prognosis factor (Five factor score (FFS)=0) have not been included in the previous studies and GC alone is considered as the reference treatment in these patients. However, as much as 50% of these patients experience relapses after a 24 months follow-up and only 40% of patients have a long lasting remission.

In the group of patients with MPA without any poor prognosis factor (FFS=0), an additional treatment with rituximab might decrease the relapse rate from 40% to 15% after an 18 months' follow-up. The efficacy and safety of this proposal must be tested.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient (male or female) over 18 year old
2. Patient agree 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 (<1 month) defined by BVAS > 0, who did not received any other treatment than glucocorticoids during last month. For patients with a BVAS<3, activity of vasculitis (either relapse or new onset) has to be confirmed by the coordinating investigator. One to 3 initial glucocorticoids pulse(s) are allowed.
6. Patient with anti-MPO antibody measured by enzyme - linked immunosorbent assay (ELISA).
7. Negative pregnancy test (serum β-hCG) for women of child-bearing potential and a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 12 months after stopping therapy

Exclusion criteria

1. Small-sized vessels vasculitis not associated to 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 hemorrhage 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 (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 in New York Heart Association classification or severe, uncontrolled cardiac disease.

15. Patients with hypersensitivity to a monoclonal antibody or biological agent.

16. Patients in a severely immunocompromised state.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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8 participants in 2 patient groups, including a placebo group

Rituximab

Experimental group

Description:

Experimental regimen: One year Glucocorticoid treatment and Rituximab IV 1 gram on Day 1 and 15

Treatment:

Drug: Rituximab

Rituximab-Placebo

Placebo Comparator group

Description:

Standard regimen: One-year Glucocorticoid treatment and Placebo-Rituximab IV on Day 1 and 15

Treatment:

Drug: placebo