AB0412 Exploratory Results from The Bliss and Illuminate Trials Support The Design of The CHABLIS-SC1 Trial, A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study To Evaluate The Efficacy and Safety of Blisibimod Administration in Subjects with Systemic Lupus Erythematosus

BackgroundTargeted, biologic inhibitors of B-cell Activating Factor (BAFF) have been evaluated in 4 large Phase 3 clinical trials in nearly 4000 patients with Systemic Lupus Erythematosus (SLE). Data from these studies identify that greatest treatment effect is discernable using more stringent endpoints in patients who enter with higher disease activity scores, taking more corticosteroids, and/or have anti-double-stranded DNA (dsDNA) and low complement C3 or C41,2,3.ObjectivesThe CHABLIS-SC1 study (NCT01395745) has completed enrollment and will be the first trial to prospectively evaluate the impact of treatment on the above “responder populations” using the BAFF inhibitor, blisibimod.MethodsCHABLIS-SC1 enrolled subjects positive for anti-nuclear and/or anti-dsDNA antibodies with SELENA-SLEDAI≥10 despite corticosteroid therapy. Subjects were randomized to have blisibimod or placebo added to their background medications. Efficacy will be evaluated using the SLE Responder Index-6 (SRI-6) at Week 52, defined as: ≥6 point reduction in SELENA-SLEDAI; no new BILAG A or 2 new BILAG B organ domain scores; and no worsening in Physician's Global Assessment.ResultsTable 1 identifies that the baseline characteristics of the 442 subjects enrolled into the CHABLIS-SC1 study more frequently meet all descriptions of “responder populations” identified previously2–7. In previous studies, the SRI-6 was associated with lower placebo responder rates and greater benefit of BAFF inhibitors over placebo.Table 1.Estimated baseline disease characteristics of subjects in the CHABLIS-SC1 study and in Phase 3 trials with other BAFF inhibitorsBlisibimodBelimumabTabalumab(CHABLIS-SC1)(BLISS Trials)(ILLUMINATE Trials)Total randomized (N)44216642288Mean age (years)36.335.340.7Female (%)93.994.191.9Mean SELENA- SLEDAI13.69.710.3Receiving corticosteroids (%)10086.375.3ANA ≥1:80 (%)98.993.0–+Anti-dsDNA (%)85.569.459.2Low C3