NCT02807103

Rituximab in Eosinophilic Granulomatosis With Polyangiitis

Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. Prospective, Randomized, Controlled, Double-blind Study

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 107 (actual)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase III, comparative, multicenter, randomized, controlled, double-blind and superiority research, comparing rituximab-based regimen with conventional therapeutic strategy for the induction of remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Patients with newly diagnosed or relapsing EGPA will be randomized in a 1:1 ratio to receive: * Experimental therapeutic strategy based on the use of rituximab (experimental group) * Conventional therapeutic strategy based on Five-Factor Score (FFS)-assessed disease severity (comparative group)

Detailed description

Systemic vasculitides are inflammatory diseases of blood vessels, among which anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are often severe with life-threatening manifestations or complications. AAV include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). Cytotoxic drugs and glucocorticoids have been the standard of care for remission induction for nearly five decades. This regimen improved the outcome of severe AAV from death to a strong likelihood of disease control and temporary remission. However, a remission is not obtained in all patients with this combination of drugs, and most patients experience disease flares requiring repeated treatment with associated significant morbidity and mortality. In 2 prospective controlled trials, rituximab, an anti-CD20 monoclonal antibody, was shown to be non inferior to cyclophosphamide to induce remission with an acceptable safety profile in patients with systemic GPA and MPA. However, patients with EGPA were not included in these trials and rituximab has not been evaluated prospectively to induce remission in this disease which pathogenesis is complex and not only restricted to ANCA responsibility. In patients with EGPA, overall survival is good when treatment is stratified according to prognostic factors (Five Factor Score) but long-term outcome is not so good since relapses occur in more than 40% of patients, leading to high cumulative morbidity and damage. In small retrospective studies, rituximab seems promising as a remission-induction agent in patients with EGPA, independently from the ANCA status. The trial detailed here is the first prospective trial evaluating rituximab as induction-remission treatment for EGPA.

Conditions

• Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Interventions

Type	Name	Description
DRUG	Rituximab	1 g intravenous pulse at day1 and day15
DRUG	Placebo-rituximab	intravenous pulses at day1 and day15
DRUG	Cyclophosphamide	intravenous 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.
DRUG	Placebo-cyclophosphamide	intravenous 7 pulses : at days 29, 50, 71, 92, 113, 134 and 155.

Timeline

• Start date: 2016-12-05
• Primary completion: 2020-10-21
• Completion: 2020-10-21
• First posted: 2016-06-21
• Last updated: 2026-01-15

Locations

1 site across 1 country: France