Zhang Hong, Wang Hong, Wei Haijing, Chen Hong, Liu Jingrui, Li Cuiyun, Zhu Xiaoxue, Li Xiaojiao, Yu Jinchen, Zhou Yinbo, Yang Xiaolei, Wang Zhaohe, Wu Min, Ding Yanhua
Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
Jilin Medical Products Administration, Jilin, China.
Front Pharmacol. 2021 Jan 25;11:609522. doi: 10.3389/fphar.2020.609522. eCollection 2020.
The study aimed to explore the bioequivalence of a proposed biosimilar BAT1806 to its reference products marketed in the EU and US (RoActemra-EU and Actemra-US) among healthy Chinese men. The tolerance, immunogenicity, and pharmacokinetics (PK) of the three drugs were also investigated. In this randomized, double-blind, single-dose, three-arm, parallel study, a single-dose of 4 mg/kg of the reference products, or the biosimilar was administered to the participants. The participants were followed up for 57 days, and PK, immunogenicity, and tolerance evaluations were completed during this period. The PK parameters were similar in all three groups: BAT1806 ( = 45), RoActemra-EU ( = 42), and Actemra-US ( = 42). The 90% confidence intervals (CIs) for the ratios of C , AUC and AUC were 86.90-104.41% for BAT1806 vs. RoActemra-EU, 91.70-106.15% for BAT1806 vs Actemra-US, and 90.04-105.53% for Actemra-US vs RoActemra-EU. For all comparisons, the 90% CIs for the C , AUC , and AUC were within the predefined bioequivalence limit of 80.00-125.00%. The intersubject variability ranged from 14.5% to 21.5%, which was considerably low. Among the participants, 19 (42.2%), 10 (23.8%), and 12 (28.6%) from the BAT1806, RoActemra-EU, and Actemra-US groups were, respectively, found to be positive for anti-drug antibodies, while 14 (31.1%), nine (21.4%), and 12 (28.6%) were positive for neutralizing antibodies. Nevertheless, these antibodies did not affect the drug concentrations, and the outcomes in the bioequivalence tests were similar after sensitivity analysis. Treatment-related and treatment-emergent adverse events (TEAEs) were recorded in 27, 34, and 32 participants in the BAT1806, RoActemra-EU, and Actemra-US groups, respectively. The most common treatment-related adverse events observed were a decrease in neutrophil, and white blood cell counts. The PK characteristics of BAT1806 were similar to those of the reference products, RoActemra-EU and Actemra-US. Both BAT1806 and the reference products exhibited low intersubject variability and similar safety profiles. http://www.chinadrugtrials.org.cn/index.html, CTR20180039; https://clinicaltrials.gov/NCT03606876.
该研究旨在探讨拟议的生物类似药BAT1806与其在欧盟和美国上市的参比产品（RoActemra-EU和Actemra-US）在健康中国男性中的生物等效性。还对这三种药物的耐受性、免疫原性和药代动力学（PK）进行了研究。在这项随机、双盲、单剂量、三臂、平行研究中，向参与者单剂量给药4mg/kg的参比产品或生物类似药。对参与者进行了57天的随访，并在此期间完成了PK、免疫原性和耐受性评估。所有三组的PK参数相似：BAT1806组（n = 45）、RoActemra-EU组（n = 42）和Actemra-US组（n = 42）。BAT1806与RoActemra-EU相比，Cmax、AUC0-t和AUC0-∞比值的90%置信区间（CI）为86.90 - 104. .41%；BAT1806与Actemra-US相比为91.70 - 106.15%；Actemra-US与RoActemra-EU相比为9 .04 - 105.53%。对于所有比较，Cmax、AUC0-t和AUC0-∞的90%CI均在预先定义的80.00 - 125.00%生物等效性限度内。受试者间变异性在14.5%至21.5%之间，相当低。在参与者中，BAT1806组、RoActemra-EU组和Actemra-US组分别有19名（42.2%）、10名（23.8%）和12名（28.6%）抗药抗体检测呈阳性，而14名（31.1%）、9名（21.4%）和12名（28.6%）中和抗体检测呈阳性。然而，这些抗体并未影响药物浓度，敏感性分析后生物等效性试验的结果相似。BAT1806组、RoActemra-EU组和Actemra-US组分别有27名、34名和32名参与者记录了与治疗相关和治疗中出现的不良事件（TEAE）。观察到的最常见的与治疗相关的不良事件是中性粒细胞和白细胞计数减少。BAT1806的PK特征与参比产品RoActemra-EU和Actemra-US相似。BAT1806和参比产品均表现出低受试者间变异性和相似的安全性概况。 http://www.chinadrugtrials.org.cn/index.html，CTR20180039；https://clinicaltrials.gov/NCT03606876 。
