Clinical Trial: Rituximab in Eosinophilic Granulomatosis With Polyangiitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomato

Brief 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 Summary:

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 pr
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Number of patients in complete remission (defined by a Birmingham Vasculitis Activity Score (BVAS) of 0 and a prednisone dose ≤7.5 mg/day ) [ Time Frame: 180 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Number of adverse events [ Time Frame: 180 days ]
  expressed as adverse events according to the CTCAE toxicity grading system per patient-year for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic 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
• Number of adverse events [ Time Frame: 360 days ]
  expressed as adverse events according to the CTCAE toxicity grading system per patient-year for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic 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
• Area under the curve for corticosteroids [ Time Frame: 180 days ]
  To measure the corticosteroid dose and to compare the corticosteroid sparing effect of rituximab versus conventional therapy
• Area under the curve for corticosteroids [ Time Frame: 360 days ]
  To measure the corticosteroid dose and to compare the corticosteroid sparing effect of rituximab versus conventional therapy
• Number of sequelae assessed by the Vasculitis Damage Index [ Time Frame: 180 days ]
• Number of sequelae assessed by the Vasculitis Damage Index [ Time Frame: 360 days ]
• ANCA titers and CD19+cells [ Time Frame: 180 days ]
• ANCA titers and CD19+cells [ Time Frame: 360 days ]
• Health Assessment Questionnaire (HAQ) score [ Time Frame: 180 days ]
  to evaluate functional disability
• Health Assessment Questionnaire (HAQ) score [ Time Frame: 360 days ]
  to evaluate functional disability
• Short Form-36 score [ Time Frame: 180 days ]
  to evaluate quality of life
• Short Form-36 score [ Time Frame: 360 days ]
  to evaluate quality of life

Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: May 20, 2016
Date Started: December 2016
Date Completion: June 2020
Last Updated: December 12, 2016
Last Verified: December 2016