Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome

Inclusion Criteria

Both cohorts must have met all the following criteria:

• Signed informed consent must be obtained prior to participation in the study
• Male or female patient >= 18 years of age
• Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2016)
• Seropositive for anti-Ro/SSA antibodies
• Stimulated whole salivary flow rate of >= 0.1 mL/min
• Able to communicate well with the Investigator to understand and comply with the requirements of the study

Inclusion criteria specific for Cohort 1:

• Screening ESSDAI value >= 5 within the following 8 organ domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematologic and biologic
• Patients with involvement of one or more of the remaining 4 domains are eligible but scores of these domains will not contribute to the assessment for eligibility for Cohort 1
• At selected sites participating in Cohort 2, patients who based on the above criterion 7, do not qualify for Cohort 1, should be further evaluated for Cohort 2
• Screening ESSPRI score of >= 5

Inclusion criteria specific for Cohort 2:

• Screening ESSDAI value = 5 or ESSPRI dryness subscore >= 5
• Hypergammaglobulinemia defined by IgG greater than upper limit of normal (ULN) or lymphocytopenia (less than lower limit of normal (LLN)) or hypocomplementemia (low C3, or low C4 - when considered due to disease activity and not due to genetic factors)
• Score of >= 30 on IDEEL symptom bother questionnaire at Screening

Exclusion Criteria

• Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness
• Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations
• Prior treatment with any of the following within 6 months prior to randomization:
• B-cell depletors (e.g. rituximab, ianalumab) unless CD19+ B cell count have returned to ≥ 50 cells/µL
• abatacept
• anti-tumor necrosis factor alpha monoclonal anti-body
• intravenous/subcutaneous Ig; plasmapheresis; i.v. or oral cyclophosphamide
• i.v. or oral cyclosporine A
• any other immunosuppressants unless explicitly allowed in criterion #5
• Use of steroids (predniso(lo)ne or equivalent corticosteroid) at dose > 10 mg/day
• Use of steroids and synthetic DMARDS at inconsistent dose and within 3 months prior to randomization