Two Arm, Double-blind, Phase III Study Assessing Efficacy and Safety of Ianalumab Versus Placebo, in Participants With Sjögren's Disease With High Symptom Burden

A Randomized, Double-blind, Placebo-controlled, 2-arm Multicenter Phase III Study to Assess the Efficacy and Safety of Ianalumab in Participants With Sjogren's Disease With High Symptom Burden (THALASSA)

The purpose of this study is to demonstrate the efficacy and safety of ianalumab (VAY736) 300 mg administered subcutaneously (s.c.) monthly for 52 weeks in adult participants with Sjögren's disease who have high symptom burden.

This is a double-blind, randomized, placebo-controlled multicenter 2-arm Phase III study, evaluating 300 mg ianalumab s.c. against placebo s.c. in adult participants with Sjögren's disease with high symptom burden.

Inclusion Criteria:

• Male or female participants ≥ 18 years of age or as per country-specific legal adult age, whichever is higher
• Classification of Sjögren's disease according to ACR/EULAR 2016 criteria.
• Seropositive for anti-Ro/SSA antibodies at screening
• SSSD oral dryness score ≥ 5 and overall SSSD summary score ≥5 collected over 14 consecutive days during the Screening 2 period
• Screening ESSDAI biologic and/or hematologic domain > 0 Note: laboratory abnormalities for scoring must be confirmed as associated with Sjögren's disease and not be due to other underlying conditions.
• Stimulated whole salivary flow (sSF) rate > 0.3 mL/min at screening
• Participants taking hydroxychloroquine (≤ 400 mg/day) are allowed to continue their medication, and must have been on a stable dose for at least 4 weeks prior to screening, which should be maintained throughout the 52 weeks of the blinded treatment period.
• Predniso(lo)ne ≤ 5 mg/day or equivalent are allowed for up to 16 weeks post-randomization.

Exclusion Criteria:

• Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness, specifically:
• Systemic sclerosis (SSc)
• Any other associated connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease)) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's disease organ domain assessments.
• Concurrent diagnosis or history of fibromyalgia or overlapping inflammatory diseases
• Prior treatment with B-cell-depleting therapy (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) within:
• 36 weeks prior to randomization, or
• As long as B-cell count is less than the lower limit of normal (LLN) or baseline value prior to receipt of previous B-cell-depleting therapy (whichever is lower) at Screening.
• Prior treatment with ianalumab
• Prior treatment with any of the following within the given period prior to Screening:
• Within 5 half-lives prior to Screening: iscalimab (anti-CD 40 mAb), belimumab (anti-BAFF mAb), abatacept (CTLA4-Fc Ig), anti-tumor necrosis factor alpha (TNFα) biologic agents, immunoglobulins (i.v./s.c.), plasmapheresis, any other investigational biologic medicines under investigation for Sjögren's disease
• Within 4 weeks OR drug-specific 5 half-lives elimination period (if longer than 4 weeks) prior to screening: i.v. or oral cyclophosphamide, mycophenolate mofetil (MMF), methotrexate, azathioprine, i.v. or oral cyclosporine A or any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors).
• History of hypersensitivity to any of the study drugs or their 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).