A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus

STUDY DESCRIPTION: This is a phase Ib study of Gusacitinib a dual inhibitor of JAK and SYK kinases, that can simultaneously target multiple signaling pathways responsible for the SLE disease pathogenesis. This study will compare the safety of Gusacitinib 80 mg with placebo initially in a double-blind period and then 80 mg daily in an open label period, followed by an off-drug period. In addition, we will have a comparator group of SLE subjects receiving standard of care treatment. We hypothesize that Gusacitinib will be safe and well tolerated in subjects with SLE. OBJECTIVES: Primary Objective: The primary Objective of the study is to determine safety and tolerability of Gusacitinib 80 mg in subjects with SLE. Secondary Objectives: Pharmacokinetics of Gusacitinib in SLE. Effects of Gusacitinib on plasma lipid profile, vascular stiffness, and endothelial dysfunction. Efficacy of Gusacitinib in controlling SLE disease activity. Exploratory objectives to understand the effects of dual JAK and SYK inhibition on Interferon Gene Signature, Serum Cytokines, NET formation, and Immune cells phenotype. ENDPOINTS: Primary Endpoint: Adverse Events severity (as defined by AEs equal or greater than grade 3 as per the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and frequency as compared to placebo at week 12. Secondary Endpoints: Change in the proportion of patients achieving SLE Responder Index-4 (SRI 4) response at week 24 compared to baseline. Another efficacy analysis will be done by comparing subjects treated with Gusacitinib vs. placebo at week 12. SRI-4 response is defined as: * Reduction of \>=4 points from baseline in SLEDAI-2K score * No new BILAG A or no more than 1 new BILAG B disease activity scores * No worsening (defined as an increase of \>=0.3 points \[10 mm\] from baseline) in the Physician s Global Assessment of Disease Activity * Change in SLEDAI-2K total score at week 24