This is a phase 2 study to evaluate the effects of sibeprenlimab 400 mg administered subcutaneously (SC) every 4 (Q4) weeks as an add-on to background treatment in participants with Sjögren's disease.

This is a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study followed by an optional open-label extension to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q4 weeks as an add-on to background treatment in participants with Sjögren's disease.

The primary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores at 28 weeks.

The key secondary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) at 28 weeks.

Approximately 80 participants who have a diagnosis of Sjögren's disease according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria will be randomized with approximately 40 participants in the sibeprenlimab group and 40 participants in the placebo group.

Key Inclusion Criteria:

• Diagnosed with Sjögren's disease.
• ESSDAI score (which measures disease activity) must be 5 or higher.
• Salivary flow rate must be at least 0.05 mL/min.
• Serum IgG level must be higher than 900 mg/dL.
• Must be able to communicate well with the investigator and agree to follow the trial requirements.
• Participants can continue certain medications (hydroxychloroquine, methotrexate, leflunomide, or azathioprine) if they have been on a stable dose for at least 30 days.
• Corticosteroid dose must be stable and no more than 10 mg/day for at least 30 days.
• Test positive for anti-Ro52 and/or anti-Ro60 antibodies.

Key Exclusion Criteria:

• Another active autoimmune rheumatic disease.
• Prior use of B-cell depleting therapy or prohibited immunosuppressants.
• Significant comorbidities including uncontrolled type 2 diabetes, malignancy, and chronic and/or acute infections.
• Suicidal ideation or behavior based on the Patient Health Questionnaire-9 (PHQ-9).

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.

Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/