phase 2a dose escalation study to investigate the safety, PK, PD, and efficacy of CC-220 in patients with SLE. Forty-two (42) adult SLE subjects fulfilling SLE ACR criteria, having a history of SLE for ≥6 months and a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥4 were randomized to placebo or 1 of 4 escalating doses of CC-220 (0.3 mg QOD, 0.3 mg QD, 0.6/0.3 mg alternating QD, or 0.6 mg QD).

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... ults: CC-220 concentration-time profiles demonstrated dose proportionality between cohorts, with moderate accumulation in the non-alternating dose cohort. CC-220 significantly reduced total CD20+ B cells by as much as 96%, immature B cells by as much as 91.2%, switched memory B cells by as much as 81.4%, BAFFR+ B cells by as much as 67.5%, and plasmacytoid dendritic cells (pDCs) by as much as 86.5% (Day 85 median percent change from baseline). Whereas reductions in B cells were observed, CD4+ as well as CD8+ T cells increased, and the rise in T cells paralleled the observed increase in plasma cells in those subjects who received the highest dose (0.6 mg). An exposure-response analysis demonstrated decreasing B cells, pDCs and neutrophils with increased exposure to CC-220. Conclusions: It was determined that 0.3 mg QD to 0.6/0.3 mg alternating QD reduced concentrations of B cells and pDC's while avoiding neutropenia. These findings, in combination with the PK, safety, and exploratory efficacy data, support continued development of CC-220 in SLE.