A Phase I Clinical Trial to Evaluate the Bioequivalence of an Adalimumab Biosimilar Adalimumab-WIBP and Humira(®).

The high costs associated with biological agents often limit accessibility for many patients, whereas biosimilars allow the wider application of biological treatment. The objectives of this phase I clinical trial were to compare the pharmacokinetics, immunogenicity, and safety profiles of the biosimilar adalimumab-WIBP and the reference product Humira® and to assess the precision of the bioequivalence evaluation. In this randomized, double-blind, parallel-group bioequivalence study, 164 healthy male Chinese participants were selected and randomly divided into two groups on a 1:1 ratio. The subjects were administered a single 40 mg subcutaneous dose of either adalimumab-WIBP or Humira®. Blood samples extracted at multiple intervals after administration were analyzed to interpret pharmacokinetic parameters, and any adverse events were documented. Alongside ensuring safety measures, the subjects were monitored for immunogenicity. The pharmacokinetic results demonstrated similar serum concentration-time curves in both groups. There were no significant differences in safety and no differences in immunogenicity profiles between the two groups. The bioequivalence was confirmed: the 90% confidence interval for the geometric mean ratio of the main pharmacokinetic parameters was within the range of 80-125%. The trial indicated the bioequivalence between adalimumab-WIBP and the reference product Humira® based on pharmacokinetics, immunogenicity, and safety profile. These findings reinforce the use of the adalimumab-WIBP biosimilar as a possible therapeutic alternative to Humira®.

Hu S ，Liu Y ，Yang L ，Yang Y ，Long F ，Bao H ，Zhang H ，Yue X ，Zhang J ，Wang Z ，Huang C ，Wang J ，Xia L ，Pan Y ，Zhang Y ，Gong F ... -  《-》

Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.

Wang W ，Zhang S ，Dou C ，Hu B ，Song H ，Qi F ，Zhao Y ，Li X ，Zhou M ，Xie J ，Deng K ，Wu Q ，Ye L ，Cui C ，Liu L ，Huang J ，Yang G ... -  《-》

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: A randomized phase I study.

Denosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel-group, two-part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double-blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60 mg. The primary endpoints were area under the serum drug concentration-time curve from time 0 to the last concentration-quantifiable time t (AUC0-t), maximum serum drug concentration (Cmax), and area under the serum drug concentration-time curve from time 0 to infinity (AUC0-inf). Twenty-four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC0-t, Cmax, and AUC0-inf between HLX14 and denosumab from different sources fell within the pre-specified similarity margins of 0.80-1.25 (AUC0-t, 0.91-1.13; Cmax, 0.91-1.13; AUC0-inf, 0.91-1.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar.

Li N ，Chu N ，Zhu L ，Wu X ，Wei Q ，Wang J ，Hu X ，Yu H ，Wang Q ，Yuan W ，Huang K ，Zhang J ... -  《-》

Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease.

Gordon M ，Taylor K ，Akobeng AK ，Thomas AG ... -  《Cochrane Database of Systematic Reviews》

A Randomized Controlled Trial of a Novel Formulation of Ketorolac Tromethamine for Continuous Infusion (NTM-001) in Healthy Volunteers.

Pergolizzi JV Jr ，Batra A ，Schmidt WK 《-》