Background Litifilimab is a humanized IgG1 monoclonal antibody targeting BDCA2, a receptor predominantly expressed on plasmacytoid dendritic cells (pDCs). In Part A of the Phase 2 LILAC study (NCT02847598), administration of litifilimab at a dose of 450 mg was superior to placebo in reducing the total active joint count at Week 24 and resulted in a greater frequency of SLE Responder Index 4 (SRI-4) responses versus placebo.¹ Two multicenter, Phase 3, randomized, double-blind, placebo-controlled studies (TOPAZ-1, NCT04895241; TOPAZ-2, NCT04961567), described here, are ongoing to further evaluate litifilimab efficacy and safety in patients with SLE.
Methods Eligible participants are randomly assigned to receive either subcutaneous litifilimab (at a high or low dose) or placebo at Weeks 0 and 2, then Q4W until Week 48 (figure 1). Appropriate representation of individuals from underrepresented populations is a focus of the TOPAZ program. The SRI-4 response at Week 52 was chosen as the primary endpoint based on its performance in Part A of the LILAC study. Multiplicity-adjusted secondary endpoints of TOPAZ-1/-2 include Joint-50 response (a 50% reduction from baseline in the active joint count, where an active joint is defined as both swollen and tender, based on a 28-joint assessment) and oral corticosteroid (OCS) tapering. Additional secondary endpoints include the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity score, Lupus Low Disease Activity State, and safety. Key features of this study design are the inclusion of several organ-specific evaluations, stringent rules for concomitant medication, and protocol-specified OCS tapering.
Results Both studies are currently recruiting, aiming to enroll 540 participants each; estimated primary completion dates are April 2025 (TOPAZ-1) and June 2025 (TOPAZ-2).
Conclusions Data from the TOPAZ studies will help characterize the efficacy and safety of litifilimab in SLE, a disease in need of greater treatment options.
Furie RA, et al. N Engl J Med 2022;387:894–904
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