BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects.
This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUC0–inf). Biosimilarity of the study drugs was confirmed if the two-sided 90% confidence interval (CI) ratios of the geometric means for the three pairwise comparisons were contained within the range 80–125%. Other pharmacokinetic parameters including area under the concentration curve to time t (AUC0–t), maximum concentration of drug in plasma (Cmax), half-life (t½), and time to Cmax (tmax) were also measured.
The pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUC0–inf was 99–112% for BAT1706 versus EU-BEV, 97–110% for BAT1706 vs US-BEV and 92–104% for EU-BEV versus US-BEV comparisons, respectively, demonstrating biosimilarity. There were no significant adverse events attributable to BAT1706, as compared to EU-BEV and US-BEV. BAT1706 demonstrated a similar safety profile to EU-BEV and US-BEV. In addition, no anti-drug antibody positive result was reported for any subject included in the study.
In this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion.
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Bio-Thera Solutions, Ltd., a biopharmaceutical company located in Guangzhou, China, provided the funding for this study.
Conflict of interest
Xiaoyun Wu is an employee of Bio-Thera Solutions. Chris Wynne is an employee of Christchurch Clinical Studies Trust, which is the contract research organization sponsored by Bio-Thera Solutions to conduct the clinical study. Chenchao Xu is an employee of Bio-Thera Solutions. Yiting Gan is an employee of Bio-Thera Solutions. Chaohe Wang is an employee of Bio-Thera Solutions. Bert E. Thomas is an employee of Bio-Thera Solutions. Jin-Chen Yu is an employee of Bio-Thera Solutions. Shengfeng Li is an employee of Bio-Thera Solutions. Li Zhang is an employee of Bio-Thera Solutions.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the Independent Ethics Committee (IEC), New Zealand. This phase I clinical trial was registered at ClinicalTrials.gov (identifier NCT03030430).
Informed consent was obtained from all individual participants included in the study.
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Wu, X., Wynne, C., Xu, C. et al. A Global Phase I Clinical Study Comparing the Safety and Pharmacokinetics of Proposed Biosimilar BAT1706 and Bevacizumab (Avastin®) in Healthy Male Subjects. BioDrugs 33, 335–342 (2019). https://doi.org/10.1007/s40259-019-00352-7