Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus

Results from a phase 1/2 randomized study

Tomomi Tsuru, Yoshiya Tanaka, Mitsumasa Kishimoto, Kazuyoshi Saito, Seiji Yoshizawa, Yoshinari Takasaki, Tomoya Miyamura, Hiroaki Niiro, Shinji Morimoto, Junichi Yamamoto, Rocio Lledo-Garcia, Jing Shao, Shuichiro Tatematsu, Osamu Togo, Takao Koike

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

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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.

元の言語英語
ページ(範囲)87-93
ページ数7
ジャーナルModern Rheumatology
26
発行部数1
DOI
出版物ステータス出版済み - 1 2 2016

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Systemic Lupus Erythematosus
Pharmacokinetics
Safety
B-Lymphocytes
Placebos
Cell Count
Immunoglobulin D
Standard of Care
epratuzumab
Area Under Curve
Down-Regulation
Fluorescence
Therapeutics

All Science Journal Classification (ASJC) codes

  • Rheumatology

これを引用

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.

:: Modern Rheumatology, 巻 26, 番号 1, 02.01.2016, p. 87-93.

研究成果: ジャーナルへの寄稿記事

Tsuru, T, Tanaka, Y, Kishimoto, M, Saito, K, Yoshizawa, S, Takasaki, Y, Miyamura, T, Niiro, H, Morimoto, S, Yamamoto, J, Lledo-Garcia, R, Shao, J, Tatematsu, S, Togo, O & Koike, T 2016, 'Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study', Modern Rheumatology, 巻. 26, 番号 1, pp. 87-93. https://doi.org/10.3109/14397595.2015.1079292
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. / Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus : Results from a phase 1/2 randomized study. :: Modern Rheumatology. 2016 ; 巻 26, 番号 1. pp. 87-93.
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title = "Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study",
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.",
author = "Tomomi Tsuru and Yoshiya Tanaka and Mitsumasa Kishimoto and Kazuyoshi Saito and Seiji Yoshizawa and Yoshinari Takasaki and Tomoya Miyamura and Hiroaki Niiro and Shinji Morimoto and Junichi Yamamoto and Rocio Lledo-Garcia and Jing Shao and Shuichiro Tatematsu and Osamu Togo and Takao Koike",
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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.

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U2 - 10.3109/14397595.2015.1079292

DO - 10.3109/14397595.2015.1079292

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