NCT06940661

Obinutuzumab for Remission Induction in Patients With Relapsing PR3-ANCA Granulomatosis With Polyangiitis

Obinutuzumab for Remission Induction in Patients With Relapsing PR3-ANCA Granulomatosis With Polyangiitis (Wegener's). Phase 2 Prospective, Open-label Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of obinutuzumab to induce clinical and serological remission in patients with relapsing PR3-ANCA granulomatosis with polyangiitis.

Detailed description

Systemic vasculitides are rare inflammatory diseases of blood vessels, among which anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are one of the most severe forms with life-threatening manifestations. In patients with AAV, the most important questions are how to achieve a long-term remission and prevent a relapse most effectively. The pivotal RAVE trial showed that rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in AAV; and could be superior than cyclophoshamide in proteinase 3 (PR3)-ANCA patients. The MAINRITSAN trial, conducted by our group (Groupe Français d'Etude des Vascularites), has then demonstrated that more AAV patients had sustained remission with rituximab than with azathioprine. However, despite its ability to induce and maintain remission, rituximab is associated with the occurrence of relapse after discontinuation in up to 50% of patients at 5-years in PR3-ANCA patients. Data strongly suggest that achieving clinical and serological remission (i.e. a BVAS (Birmingham Vasculitis Activity Score) of 0 and a negativation of ANCA) and longer B-cell depletion could be major goals to achieve in PR3-ANCA granulomatosis with polyangiitis to decrease the risk of relapse. Obinutuzumab is a humanized type 2 antibody targeted against CD20. In preclinical studies, obinutuzumab showed superior efficacy, as compared with rituximab. In clinical studies, obinutuzumab was shown to be superior to rituximab in patients with chronic lymphocytic leukemia and follicular lymphoma, and met its primary and secondary endpoints in lupus nephritis. The OBI-WAN study aims to evaluate the efficacy and safety of obinutuzumab to induce clinical and serological remission in patients with relapsing PR3-ANCA granulomatosis with polyangiitis. We hypothesize that obinutuzumab would induce higher remission rates and subsequent longer B-cell depletion compared to what is described for rituximab.

Conditions

• Granulomatosis With Polyangiitis

Interventions

Type	Name	Description
DRUG	Obinutuzumab	Patient will receive 1000 milligrams intravenous (IV) infusion on week 0, week 2, week 24 and week 26. Patients will receive the same standardized glucocorticoid tapering schedule (prescribe as a standard of care management and considered as auxiliary medicinal product) Premedication for obinutuzumab infusion related reactions (considered as auxiliary medicinal products) : * 100 mg methylpredinisolone * 1000 mg paracetamol * 5 mg dexchlorpheniramine

Timeline

• Start date: 2025-12-19
• Primary completion: 2027-12-01
• Completion: 2028-07-01
• First posted: 2025-04-23
• Last updated: 2026-03-06

Locations

1 site across 1 country: France