A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers

ABSTRACT

Background

Humira® is a fully humanized anti-tumor necrosis factor (TNF-α) monoclonal antibody that has been marketed and approved in the United States for the clinical treatment of rheumatoid arthritis (RA), ankylosing spondylitis, psoriasis and other immune-mediated diseases. This study compared the bioequivalence, immunogenicity and safety of adalimumab injecta (a biosimilar of Humira® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Humira® in healthy Chinese male subjects in a phase I clinical study.

Methods

Healthy Chinese male subjects (N = 164) were randomly given a subcutaneous injection of 40 mg adalimumab or Humira® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and primary pharmacokinetic (PK) parameters were statistically analyzed. To evaluate drug immunogenicity, anti-drug antibody (ADA) and neutralizing antibody (nAb) levels were detected. To evaluate the safety of the drugs, the subjects’ physical indicators, such as multiple vital signs and routine blood tests, were continuously monitored.

Results

The similarity ratios of adalimumab and Humira® PK parameters were all within 80%-125%, meeting the bioequivalence standards. Drug-induced ADA and nAb levels were similar, and the drug safety in subjects was also similar.

Conclusions

All study drugs showed similar bioequivalence, immunogenicity and safety.

Clinical trial registration

CTR20182070 (Chinese Clinical Trial Registry)

KEYWORDS:

• Adalimumab injecta
• bioequivalence
• biosimilar
• Humira®
• pharmacokinetic

Acknowledgments

The authors would like to thank all those involved in this study, including the volunteers and investigators who conducted the study.

Declaration of interest

Zhenyue Gao and Zhongnan Xu are employees of Chia Tai Tianqing Pharmaceutical Group Co.,Ltd; Yanli Wang, Zhengzhi Liu, Guangwen Liu, Xinyao Qu, Jiahui Chen, and Haimiao Yang are employees of Affiliated Hospital of Changchun University of Chinese Medicine; and Xinran Ren is a graduate student of Jilin University. Phase I Clinical Trial Laboratory, Affiliated Hospital of Changchun University of Chinese Medicine is the research organization to carry out the clinical trial. And Shanghai Xihua Scientific Co., Ltd. carried out the detection of plasma drug concentration, including ADA and nAb in blood samples. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Author contributions

Yang HM and Xu ZN were involved in the conception and design of this research; Wang YL, Gao ZY, Liu ZZ, Qu XY, and Chen JH performed the research; Gao ZY, Liu ZZ and Ren XR analyzed the data and wrote the manuscript; Yang HM and Xu Zn finally approved of the version to be published. And that all authors agree to be accountable for all aspects of the work.

Data availability statement

We confirm that the figures and tables in the manuscript are original and have not been published before. The data that support the findings of this study are available from the corresponding author upon reasonable request but remain subject to all applicable legal requirements to protect the confidentiality of the study participants’ personal information.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The trial was funded by Chia Tai Tianqing Pharmaceutical Group Co.,Ltd. The founder helps pay for this study and has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.