TY - JOUR
T1 - Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus
T2 - Results from a phase 1/2 randomized study
AU - Tsuru, Tomomi
AU - Tanaka, Yoshiya
AU - Kishimoto, Mitsumasa
AU - Saito, Kazuyoshi
AU - Yoshizawa, Seiji
AU - Takasaki, Yoshinari
AU - Miyamura, Tomoya
AU - Niiro, Hiroaki
AU - Morimoto, Shinji
AU - Yamamoto, Junichi
AU - Lledo-Garcia, Rocio
AU - Shao, Jing
AU - Tatematsu, Shuichiro
AU - Togo, Osamu
AU - Koike, Takao
N1 - Publisher Copyright:
© 2015 Japan College of Rheumatology.
PY - 2016/1/2
Y1 - 2016/1/2
N2 - Objectives: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.Methods: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.Results: Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. Cmax and AUCτ increased proportionally with dose after first and last infusion, t1/2 was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19+CD22+) and unswitched memory B cells (CD19+IgD+CD27+). Small-to-moderate decreases were observed in total B cell (CD20+) count.Conclusions: Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.
AB - Objectives: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.Methods: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.Results: Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. Cmax and AUCτ increased proportionally with dose after first and last infusion, t1/2 was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19+CD22+) and unswitched memory B cells (CD19+IgD+CD27+). Small-to-moderate decreases were observed in total B cell (CD20+) count.Conclusions: Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.
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U2 - 10.3109/14397595.2015.1079292
DO - 10.3109/14397595.2015.1079292
M3 - Article
C2 - 26382733
AN - SCOPUS:84952637124
VL - 26
SP - 87
EP - 93
JO - Modern Rheumatology
JF - Modern Rheumatology
SN - 1439-7595
IS - 1
ER -