Pharmacokinetics, Pharmacodynamics and Safety of Belimumab in Chinese Patients with Systemic Lupus Erythematosus: A Phase I, Open-Label Study

Jing Zhang; Weiguo Wan; Liyan Miao; Jian Wu; Jun Dong; Yinghua Shen; Cui Xiong; Chao Li; Yu Xue; Guoying Cao; Peiming Ma

doi:10.1007/s40744-020-00193-9

Pharmacokinetics, Pharmacodynamics and Safety of Belimumab in Chinese Patients with Systemic Lupus Erythematosus: A Phase I, Open-Label Study

Rheumatol Ther. 2020 Mar;7(1):191-200. doi: 10.1007/s40744-020-00193-9. Epub 2020 Jan 17.

Authors

Jing Zhang¹, Weiguo Wan², Liyan Miao³, Jian Wu³, Jun Dong⁴, Yinghua Shen⁴, Cui Xiong⁴, Chao Li⁵, Yu Xue², Guoying Cao¹, Peiming Ma⁶

Affiliations

¹ Phase I Clinical Trial Center, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
² Department of Rheumatology, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
³ The National Institution of Drug Clinical Trial & Laboratory of Phase I Clinical Study, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁴ GlaxoSmithKline, Shanghai, China.
⁵ Novartis Pharma, Shanghai, China.
⁶ GlaxoSmithKline, Shanghai, China. peiming.p.ma@gsk.com.

Abstract

Introduction: The B cell survival factor B lymphocyte stimulator (BLyS) is elevated in patients with systemic lupus erythematosus (SLE) and associated with disease activity. Belimumab, a monoclonal antibody specific for soluble BLyS, is approved for the treatment of adults with active, autoantibody-positive SLE receiving standard therapy. Ethnicity is one of the factors that can potentially affect the pharmacokinetics (PK) of therapeutic monoclonal antibodies, and therefore their efficacy and safety.

Methods: This phase 1, open-label study (200909) evaluated the pharmacokinetics (PK, primary objective), pharmacodynamics (PD), and safety (secondary objectives) of belimumab in Chinese patients with SLE (N = 20). Blood samples were taken up to 84 days after a single intravenous (IV) dose of belimumab 10 mg/kg.

Results: Peak serum concentrations of belimumab (C_max) were obtained within the 1-h infusion. Geometric mean C_max, area under the concentration-time curve (time 0 to last quantifiable concentration), terminal half-life, systemic clearance, and volume of distribution were 221 μg/mL, 2395 day·μg/mL, 14.6 days, 4.06 mL/day/kg, and 85.7 mL/kg, respectively. Decreases in CD20⁺, CD20⁺/CD27^- naïve, CD20⁺/CD69⁺ active, CD20⁺/CD138⁺ plasmacytoid, CD19⁺/CD27^BRIGHT/CD38^BRIGHT SLE subset, and CD20^-/CD138⁺ plasma B Cells post-dose were accompanied by an increase in CD20⁺/CD27⁺ memory B cells. Four cases of upper respiratory tract infection (three mild, one moderate) and one case of mild pharyngitis were possibly drug-related; all resolved during the study.

Conclusion: PK of a single belimumab 10 mg/kg IV dose in Chinese patients with SLE were similar to those observed previously in Japanese and American (white and African-American) patients with SLE. PD results were consistent with belimumab inhibiting BLyS, and belimumab was well tolerated. These data support the use of belimumab in Chinese patients with SLE.

Trial registration: ClinicalTrials.gov identifier, NCT02880852.

Keywords: Belimumab; Chinese ethnicity; Pharmacodynamics; Pharmacokinetics; Systemic lupus erythematosus.

Associated data

ClinicalTrials.gov/NCT02880852