OBI-WAN : Obinutuzumab for remission induction in patients with relapsing PR3-ANCA granulomatosis with polyangiitis (Wegener’s). Phase 2 prospective, open-label study

The primary objective of this study is to evaluate the **efficacy** of obinutuzumab in patients with relapsing PR3-ANCA granulomatosis with polyangiitis (Wegener’s) at week 24. This is clinically relevant as it aims to determine the percentage of patients achieving a Birmingham Vasculitis Activity Score (BVAS) of 0, the negativation of PR3-ANCA, and the successful discontinuation of corticosteroid treatment following the completion of a prednisone taper. These outcomes are critical for assessing the potential of obinutuzumab to induce remission in this patient population.

The secondary objectives include: - Determining the **safety** of obinutuzumab by analyzing the proportion of participants experiencing adverse events and severe adverse events. - Determining the rate of mortality. - Determining the rate of disease flares, including minor and major relapses. - Determining the rate of BVAS of 0 during treatment with prednisone at a dose of less than 10 mg per day at 6 months. - Determining the duration of B-cell depletion after obinutuzumab. - Evaluating the impact on the quality of life and other patient-reported outcomes (PRO) of obinutuzumab at week 24 and 52. - Determining sequelae assessed by the Vasculitis Damage Index at week 24 and 52.

The clinical trial involves participants diagnosed with **PR3-ANCA granulomatosis with polyangiitis (Wegener’s)**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have an active disease, as indicated by a Birmingham Vasculitis Activity Score (BVAS) of 3 or higher. The trial does not include a vulnerable population. Participants must be within the first 21 days following the initiation or increase of glucocorticoids at a dose of 1 mg/kg/day or less. The selection criteria ensure that all participants are capable of providing written informed consent and have an affiliation with a mode of social security. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **obinutuzumab** in patients with relapsing PR3-ANCA granulomatosis with polyangiitis, also known as Wegener's granulomatosis. This is a Phase 2, prospective, open-label study. The trial aims to assess the percentage of patients achieving clinical and serological remission at week 24, defined by a Birmingham Vasculitis Activity Score (BVAS) of 0, negativation of PR3-ANCA, and successful discontinuation of corticosteroid treatment following a prednisone taper. The study will also monitor secondary endpoints, including adverse events, vasculitis relapses, and patient-reported outcomes over a 12-month period.

Participants will be involved in the study for a total duration of 12 months. The trial will commence with a screening visit to confirm eligibility based on criteria such as age, disease activity, and ability to provide informed consent. Eligible participants will then undergo a series of study visits, including baseline assessments, regular follow-up visits at specified intervals, and an end-of-study visit. The follow-up visits will be conducted at weeks 24 and 52 to evaluate the primary and secondary endpoints, including the assessment of adverse events and patient-reported outcomes.

The trial is expected to start recruiting participants on June 3, 2025, and is estimated to conclude by July 14, 2028. Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The study will utilize **Gazyvaro 1,000 mg concentrate for solution for infusion**, administered intravenously, with a maximum daily dose of 1,000 mg and a total dose not exceeding 4,000 mg over the treatment period. The trial is not classified as low intervention, and the investigational medicinal product is used outside its marketing authorization. The study is conducted under the sponsorship of Roche Registration GmbH.

The clinical trial involves the administration of **Gazyvaro**, a pharmaceutical product containing the active substance **obinutuzumab**. Gazyvaro is formulated as a **concentrate for solution for infusion** and is intended for **intravenous use**. The dosage regimen for this trial specifies a maximum daily dose of 1,000 mg, with a total maximum dose of 4,000 mg over the course of the treatment. The treatment period is set for a maximum of 26 weeks. Obinutuzumab is a protein-based therapeutic agent, classified under the ATC code L01XC15, and is produced by Roche Registration GmbH. The product is not a pediatric formulation and has been designated as an orphan drug under the number EU/3/15/1504.

In this study, Gazyvaro is used as the experimental medication to evaluate its efficacy in inducing remission in patients with relapsing PR3-ANCA granulomatosis with polyangiitis, commonly known as Wegener's granulomatosis. The trial is designed as a Phase 2, prospective, open-label study. The primary objective is to assess the efficacy of obinutuzumab at week 24, defined by achieving a Birmingham Vasculitis Activity Score (BVAS) of 0, negativation of PR3-ANCA, and successful discontinuation of corticosteroid treatment following a prednisone taper.

Participants' compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. The study focuses solely on the administration of the experimental medication, Gazyvaro, to determine its therapeutic potential in the specified patient population.

The efficacy of obinutuzumab in patients with relapsing PR3-ANCA **granulomatosis with polyangiitis** will be assessed at week 24 (month 6) of the clinical trial. The primary efficacy endpoints include the percentage of patients achieving a Birmingham Vasculitis Activity Score (BVAS) of 0, the negativation of PR3-ANCA, and the successful discontinuation of corticoids treatment following the completion of the prednisone taper. These parameters will be measured to determine clinical and serological remission.

Secondary efficacy endpoints will be evaluated at both week 24 and week 52. These include the number of adverse events per patient-year, the number and causes of deaths over the 12-month study period, and the proportion of participants experiencing vasculitis relapses. Additional secondary endpoints involve the proportion of participants maintaining a BVAS of 0 while on a prednisone dose of less than 10 mg per day, the time to B-cell repopulation as indicated by detectable CD19+ B cells in peripheral blood, and patient-reported outcomes (PRO) such as the Health Assessment Questionnaire (HAQ) and SF-36. The Vasculitis Damage Index will also be assessed at these timepoints.