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.

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.