Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 87-93 |
| Number of pages | 7 |
| Journal | Modern Rheumatology |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2 2016 |
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All Science Journal Classification (ASJC) codes
- Rheumatology
Cite this
Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus : Results from a phase 1/2 randomized study. / Tsuru, Tomomi; Tanaka, Yoshiya; Kishimoto, Mitsumasa; Saito, Kazuyoshi; Yoshizawa, Seiji; Takasaki, Yoshinari; Miyamura, Tomoya; Niiro, Hiroaki; Morimoto, Shinji; Yamamoto, Junichi; Lledo-Garcia, Rocio; Shao, Jing; Tatematsu, Shuichiro; Togo, Osamu; Koike, Takao.
In: Modern Rheumatology, Vol. 26, No. 1, 02.01.2016, p. 87-93.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84952637124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84952637124&partnerID=8YFLogxK
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 -