A Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren's Syndrome

An Adaptive Phase 2 Randomized Double-blind, Placebo-controlled Multi-center Study to Evaluate the Safety and Efficacy of Multiple LOU064 Doses in Patients With Moderate to Severe Sjögren's Syndrome (LOUiSSe)

This was an adaptive design phase 2 study to establish safety and efficacy; and to characterize the dose-response of LOU064 in subjects with moderate to severe Sjögren's syndrome. LOU064 is an oral Bruton's tyrosine kinase (BTK) inhibitor.

This study was planned as an adaptive Phase 2 randomized, double-blind, placebo-controlled, multi-center, integrated dose-ranging study to evaluate the safety and efficacy of multiple remibrutinib doses in patients with moderate to severe Sjögren's Syndrome.

Of the initially planned two parts, only Part 1 of the study was conducted. In Part 1, the highest expected biologically active single dose of remibrutinib (100 mg) was tested in two different dosing regimens, a once daily dose (qd) or twice daily dose (bid), and compared to the placebo group. Each patient in Part 1 of the study underwent a screening period of up to 6 weeks, a treatment period of 24 weeks, and a follow-up period of 30 days post-treatment before the End of Study (EOS) visit. The total duration for each patient in the study, including Screening, was up to 35 weeks. For the treatment period, patients were randomized in a 1:1:1 ratio to one of the 3 treatment groups: remibrutinib 100 mg bid, remibrutinib 100 mg qd and placebo.

Inclusion Criteria:

• Diagnosis of SjS according to the 2016 ACR/EULAR criteria
• Screening ESSDAI (based on weighted score) ≥ 5 derived from 8 domains
• Screening ESSPRI ≥ 5
• Seropositive for anti-Ro/SSA antibodies at or within 3 months prior to screening
• Unstimulated salivary flow > 0 mL/min.

Exclusion Criteria:

• Sjögren's Syndrome overlap syndromes with another autoimmune disease as primary illness
• DMARDs or kinase inhibitors within 3 months prior to baseline above certain doses OR maintained during study
• Rituximab or other B cell depleting drug within 12 months of Screening .
• Current use of prednisone or equivalent > 15mg/d or dose change within 2 weeks prior to Screening
• Use of medication known to cause, as a major side effect, dry mouth / eyes
• HIV, Hepatitis C, Hepatitis B, known or suspected history of an ongoing, chronic or recurrent infectious disease such as tuberculosis