Pharmacokinetics, safety, and immunogenicity of HLX03, an adalimumab biosimilar, compared with reference biologic in healthy Chinese male volunteers: Results of a randomized, double-blind, parallel-controlled, phase 1 study

Hong Zhang, Min Wu, Jixuan Sun, Xiaoxue Zhu, Cuiyun Li, Yanhua Ding, Xiaodi Zhang, Katherine Chai, Xiaojiao Li, Hong Zhang, Min Wu, Jixuan Sun, Xiaoxue Zhu, Cuiyun Li, Yanhua Ding, Xiaodi Zhang, Katherine Chai, Xiaojiao Li

Abstract

The primary objective of this randomized, double-blind, parallel-controlled study (from December 2016 to October 2018) was to evaluate pharmacokinetic (PK) equivalence of adalimumab biosimilar HLX03 and reference adalimumab in healthy volunteers, and to assess safety, and immunogenicity of HLX03. The primary PK endpoints were maximum observed plasma concentration (Cmax ) and area under the concentration curve from time zero to the last quantifiable concentration (AUC0-t ). Equivalence was determined if the 90% confidence interval (CI) of geometric least square mean ratio between the two treatment groups were within the predefined range of 80%-125%. Safety and immunogenicity were monitored during the study. Healthy Chinese males (N = 220) were randomized 1:1 to receive a single subcutaneous 40 mg dose of HLX03 or China (CN)-sourced adalimumab. The ratios of the geometric mean of Cmax and AUC0-t were 102.2% and 105.7%, respectively, with corresponding 90% CIs falling in the predefined margins, which demonstrated PK equivalence between HLX03 and CN-adalimumab. The incidence of treatment-emergent adverse events (TEAEs) was similar in the two groups (73.8% and 66.0% in the HLX03 and CN-adalimumab groups, respectively). Grade 3-4 TEAEs were reported in 7.5% and 5.7% of participants, respectively. The incidences of participants with antidrug antibodies (HLX03: 96.2%; CN-adalimumab: 93.4%) or neutralizing antibodies (HLX03: 40.6%, CN-adalimumab: 41.4%) were comparable between groups. This study demonstrated PK bioequivalence between HLX03 and CN-adalimumab, with similar safety and immunogenicity profiles. These data support further clinical development of HLX03 as an adalimumab biosimilar.

Trial registration: ClinicalTrials.gov NCT03357939.

Keywords: adalimumab; bioequivalence; biosimilar; pharmacokinetics.

Conflict of interest statement

Xiaodi Zhang and Katherine Chai are employees of Shanghai Henlius Biotech, Inc. All other authors have no conflict of interest.

© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Figures

FIGURE 1
FIGURE 1
Participants disposition summary. CN‐adalimumab, China‐sourced adalimumab; PK‐FAS, pharmacokinetic full analysis set; PK‐PPS, pharmacokinetic per protocol set
FIGURE 2
FIGURE 2
Mean plasma concentration–time curves (A) linear scale (B) semi‐logarithmic scale following a single subcutaneous injection of 40 mg HLX03 and CN‐adalimumab (PK‐PPS). CN‐adalimumab, China‐sourced adalimumab; PK‐PPS, pharmacokinetic per protocol set
FIGURE 3
FIGURE 3
Development of (A) ADAs and (B) NAbs in healthy participants after a single dose of HLX03 or CN‐adalimumab.The positive rate of binding antibody assay was calculated with the number of participants in the analysis set as the denominator; the positive rate of neutralizing antibody was calculated with the number of ADA‐positive participants as the denominator. ADA, antidrug antibody; CN‐adalimumab, China‐sourced adalimumab; NAb, neutralizing antibody

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