OBINUTUZUMAB for Granulomatosis with polyangiitis (Wegener's)|PR3-ANCA positive granulomatosis with polyangiitis

Inclusion criteria

• {"criterion_text":"- Patient aged of 18 years or older\n- Patients with relapsing granulomatosis with polyangiitis positive for PR3-ANCA at inclusion, according to the ACR/EULAR 2022 classification criteria, and/or the 2012 revised Chapel Hill Consensus Conference definition.\n- Patients with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥ 3\n- Patients within the first 21 days following initiation/increase of glucocorticoids at a dose ≤1 mg/kg/day\n- Patient able to give written informed consent prior to participation in the study\n- Affiliation with a mode of social security (profit or being entitled)"}

Exclusion criteria

• {"criterion_text":"- Patients with MPO-positive AAV, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,\n- Patients unable to give written informed consent prior to participation in the study.\n- Patients with vasculitis in remission of the disease defined as a BVAS < 3,\n- Patients with a newly-diagnosis of GPA\n- Patients treated with rituximab within the last 6 months before inclusion,\n- Patients treated with cyclophosphamide within the last 6 months before inclusion,\n- Patients with severe cardiac failure defined as class IV in New York Heart Association\n- Subject known to be seropositive for human immunodeficiency virus (HIV), hepatitis B (included history of previous infection) or hepatitis C,\n- Patients with active cancer or recent cancer (< 5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,\n- Patients with hypersensitivity to a monoclonal antibody or biologic agent,\n- Patients with severe liver insufficiency (prothrombin time <50% and total bilirubin >50 micrmol/L) or pulmonary insufficiency requiring nasal oxygen\n- Patients with hypersensitivity to obinutuzumab or to its excipients,\n- Patients with an active infection or a history of chronic or recurrent infections\n- Vaccination with live virus vaccines in the 4 weeks before study enrolment\n- Contra-indications to auxiliary medicinal products (methylprednisolone, paracetamol, prednisone, dexchlorpheniramine),\n- Patients with other uncontrolled diseases that could interfere with participation in the trial according to the protocol,\n- Patients suspected not to be observant to the proposed treatments,\n- Pregnant women and lactation,\n- Men who refuse to use effective method of contraception (condom) from the date of consent through the end of the study and at least 18 months after stopping obinutuzumab,\n- Patient participating in another investigational therapeutic study,\n- Protected adults (including individual under legal guardianship by court order or curatorship) or adults deprived of liberty,"}

Primary endpoints

• {"endpoint_text":"- The percentage of patients who achieved clinical and serological remission at week 24 (month 6), defined by: 1) a BVAS of 0; 2) a negativation of PR3-ANCA; 3) a successful completion of the prednisone taper","definition_or_measurement_approach":"Clinical and serological remission at week 24 (month 6) defined by: (1) BVAS of 0, (2) negativation of PR3-ANCA (serology conversion to negative), and (3) successful completion/discontinuation of prednisone according to the predefined prednisone taper schedule."}

Secondary endpoints

• {"endpoint_text":"- The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at week 24 and 52 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","definition_or_measurement_approach":"Adverse events counted and graded by CTCAE; expressed per patient-year at weeks 24 and 52 for the listed event types (including death, specified grade thresholds, malignancies, VTE, hospitalizations, infusion reactions within 24 hours)."}
• {"endpoint_text":"- Number and causes of deaths over the 12 months study period","definition_or_measurement_approach":"Count of deaths during the 12-month study period with documentation of cause(s)."}
• {"endpoint_text":"- Proportion of participants who had vasculitis relapses (BVAS > 0), including minor and major relapses over the 12 months study period","definition_or_measurement_approach":"Proportion of participants with BVAS > 0 at any time during the 12-month study period, categorized into minor and major relapses as per protocol definitions."}
• {"endpoint_text":"- Proportion of participants who remain with a BVAS of 0 during the treatment period with prednisone at a dose of less than 10 mg per day","definition_or_measurement_approach":"Proportion of participants maintaining BVAS = 0 while on prednisone <10 mg/day during the treatment period (assessed at specified visits, e.g., 6 months)."}
• {"endpoint_text":"- The time to B-cell repopulation defined by detectable CD19+ B cells in peripheral blood over the 12 months study period","definition_or_measurement_approach":"Time from treatment to first detection of CD19+ B cells in peripheral blood (repopulation), assessed over 12 months."}
• {"endpoint_text":"- The patient-reported outcomes (PRO) including HAQ and SF-36, patient-reported disease activity, anxiety and depression, burden of the disease and treatment and adherence to treatment, at week 24 and 52","definition_or_measurement_approach":"PRO instruments (HAQ, SF-36 and other patient-reported measures) administered at weeks 24 and 52; scores and changes from baseline analyzed."}
• {"endpoint_text":"- The Vasculitis Damage Index at week 24 and 52","definition_or_measurement_approach":"VDI score assessed at weeks 24 and 52 to evaluate disease sequelae/damage."}

France

Earliest CTIS Part Ii Submission Date

14-02-2025

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

304

Number Of Sites

28

Number Of Participants

36

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France