Evaluation of Obinutuzumab-Induced Depletion of Autoreactive B Cells in Affected Tissues of Patients with Sjögren's Syndrome

The primary objective is to evaluate whether obinutuzumab induces the depletion of anti-nuclear antibody producing and rheumatoid factor B cells within the affected tissues of patients diagnosed with Sjögren's syndrome. This study assesses the pharmacodynamic impact of the agent on specific B cell populations relevant to the pathophysiology of the disease. Secondary objectives include:

• Assessment of the potential clinical effect of obinutuzumab in patients with Sjögren's syndrome.
• Analysis of the indirect effects of the treatment on other inflammatory cell populations in affected tissues.
• Evaluation of the effects of obinutuzumab on aberrant clonally expanded B cells in affected tissues.

The sponsor did not provide information regarding the total number of participants. The study population consists of adults with Sjögren's syndrome. The cohort includes both male and female individuals. Inclusion requires meeting the EULAR/ACR 2016 classification criteria for primary disease. Eligible participants must demonstrate the presence of anti-nuclear antibody, anti-Ro60, or anti-La. Specific requirements involve the presence of cryoglobulinemia or predictors for lymphoproliferative disease, such as rheumatoid factor, lymphadenopathy, salivary gland swelling, purpuric lesions, vasculitis, or a high lymphocytic focus score. For female patients of childbearing potential, the use of effective contraception is required.

This phase 4 clinical trial is designed to evaluate the efficacy of obinutuzumab in the depletion of anti-nuclear antibody producing and rheumatoid factor B cells within the affected tissues of patients diagnosed with Sjögren's syndrome. The study methodology involves the administration of the investigational product via intravenous infusion. The research process begins with a screening visit to confirm eligibility based on the EULAR/ACR 2016 classification criteria and the presence of specific autoantibodies, including anti-Ro60 and anti-La. Participants may be required to undergo tissue biopsies of the salivary glands or lymph nodes to facilitate the primary endpoint analysis. Following the initiation of treatment, follow-up assessments will be conducted at various intervals, including weeks 12, 24, and 36, to monitor changes in the ESSDAI score, PhGA, PaGA, and ESSPRI. The primary endpoint focuses on the depletion of specific B cells in the blood and inflamed tissues compared to baseline measurements at 3 months. Total study activities are estimated to occur within a recruitment and observation period spanning from 2026 to 2028.

The investigational product is obinutuzumab, provided as Gazyvaro. This substance is administered in the form of a solution for infusion. The dosage is 1000 mg, which is delivered via intravenous infusion.

The efficacy of obinutuzumab will be assessed through several parameters. The primary endpoint is the depletion of anti-Ro60, anti-Ro52, anti-La, and rheumatoid factor B cells within the blood, inflamed salivary gland, and involved lymph node at 3 months following treatment initiation, compared to baseline measurements.

Secondary efficacy assessments include:

• Change from baseline in the ESSDAI score at weeks 12, 24, and 36.
• Proportion of patients achieving a reduction of ≥3 points from baseline in the ESSDAI score at weeks 12, 24, and 36.
• Proportion of patients achieving an ESSDAI score <5 at weeks 12, 24, and 36.
• Change from baseline in PhGA of disease activity at weeks 12, 24, and 36.
• Change from baseline in PaGA of disease activity at weeks 12, 24, and 36.
• Proportion of patients achieving a reduction of ≥1 point or 15% from baseline in the ESSPRI at weeks 12, 24, and 36.
• Change from baseline in STAR, Schirmer’s test, and unstimulated whole saliva secretion.