Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome

Inclusion criteria

Signed informed consent must be obtained prior to participation in the study
Women and men ≥ 18 years of age
Classification of Sjögren's syndrome according to the ACR/EULAR 2016 criteria
Time since diagnosis of Sjögren's of ≤ 7.5 years at screening

Positive anti-Ro/SSA antibody at screening

Patients negative for anti-Ro/SSA antibody are eligible, if they have a positive salivary gland biopsy confirmed by central expert review
Enrollment of anti-Ro/SSA-negative patients will be limited up to ≤10% of the study population
Screening ESSDAI score of ≥ 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic.
Stimulated whole salivary flow (sSF) rate of ≥ 0.05 mL/min at screening
Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study
Patients taking hydroxychloroquine (≤ 400 mg/day), methotrexate (≤ 25 mg/week) or azathioprine (≤ 150 mg/day) alone or in combination, are allowed to continue their medication, and must have been on a stable dose for at least 30 days prior to randomization.
Patients taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day predniso(lo)ne or equivalent for at least 30 days before randomization.

Patients taking

disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed in inclusion criterion #9 or
the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterium glycosides (TG)
must discontinue these medications at least 30 days prior to randomization, except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed.

Exclusion Criteria:

Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer3. Prior treatment with ianalumab
Prior use of a B-cell depleting therapy other than ianalumab within 36 weeks prior to randomization or as long as B-cell count is <50 cells/μL
Prior treatment with any of the following within 6 months prior to randomization:
iscalimab, belimumab , abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins plasmapheresis; i.v. or oral cyclophosphamide and mycophenolate mofetil, i.v. or oral cyclosporine A; any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors) unless explicitly allowed by protocol
Use of corticosteroids (predniso(lo)ne or equivalent corticosteroid) at dose >10 mg/day

Any one of the following laboratory values at screening:

Hemoglobin levels < 8.0 g/dL
White blood cells (WBC) count < 2.0 x 10E3/µL
Platelet count < 80 x 10E3/µL
Absolute neutrophil count (ANC) < 0.8 x 10E3/µL
Active viral, bacterial or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug formulation (sucrose, L-histidine hydrochloride/ L-histidine, polysorbate 20)
History of major organ, hematopoietic stem cell or bone marrow transplant
Required regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study.
Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the study
Receipt of live/attenuated vaccine within a 4-week period prior to randomization
History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer or Sjögren's related lymphoma), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
History of sarcoidosis
Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes mellitus), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study
Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the subject.
Evidence of active tuberculosis (TB) infection (after anti-TB treatment, patients with history of or latent TB may become eligible according to national guidelines)
Pregnant or nursing (lactating) women,
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational medication.
Patients with a known history of non-compliance to medication, or who were unable or unwilling to complete PRO questionnaires, or who are unable or unwilling to use the device for collection of PROs.