Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
Qyuns Therapeutic Co. Ltd., Taizhou City, Jiangsu Province, China.
Ann Med. 2021 Dec;53(1):375-383. doi: 10.1080/07853890.2021.1887925.
QX003S is a biosimilar candidate for the reference tocilizumab, Actemra®. We investigated the tolerance, variability, and pharmacokinetics (PK) of QX003S biosimilar in healthy Chinese male subjects.
A randomised, double-blind, two-arm, parallel study was performed to examine the bioequivalence of QX003S (8 mg/kg) with that of Actemra® as a reference drug.
QX003S ( = 40) and Actemra® ( = 40) groups exhibited similar PK properties. The inter-subject variability ranged from 14.95% to 18.78%. The 90% confidence intervals of the ratios for C, AUC andAUC in both groups were within the range of 80-125%. After administration, the number of subjects who tested positive for anti-drug antibodies (ADA) in the QX003S group and Actemra® groups was 6 (14.3%) and 14 (34.1%), respectively. Adverse reactions occurred in 100% and 97.6% subjects in the QX003S and Actemra® groups, respectively. The most common adverse reactions were decrease in fibrinogen level and neutrophil and leukocyte counts.
The PK characteristics and immunogenicity exhibited by QX003S were similar to that of the reference product, Actemra®. The safety profile was similar in the two treatment groups with mild-moderate adverse effects.Trial RegistrationThe trial is registered at Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html#CTR20190002)Key pointsThis was the first clinical report of a new proposed tocilizumab biosimilar, QX003S.This phase-I randomized, controlled study compared pharmacokinetics, variability,immunogenicity, and safety of QX003S vs. the approved tocilizumab product (Actemra@).The results demonstrate bioequivalence between BAT1806 and the reference products (Actemra@), as well as comparable immunogenicity, safety and tolerability profiles.
QX003S 是一种参照托珠单抗（Actemra®）的生物类似药候选药物。我们研究了健康中国男性受试者中 QX003S 生物类似药的耐受性、变异性和药代动力学（PK）。
进行了一项随机、双盲、双臂、平行研究，以检查 QX003S（8mg/kg）与作为参比药物的 Actemra®的生物等效性。
QX003S（n=40）和 Actemra®（n=40）组表现出相似的 PK 特性。个体间变异性范围为 14.95%至 18.78%。两组的 C、AUC 和 AUC 的比值 90%置信区间均在 80-125%范围内。给药后，在 QX003S 组和 Actemra®组中检测到抗药物抗体（ADA）阳性的受试者人数分别为 6（14.3%）和 14（34.1%）。QX003S 组和 Actemra®组的不良反应发生率均为 100%和 97.6%。最常见的不良反应是纤维蛋白原水平以及中性粒细胞和白细胞计数降低。
QX003S 的 PK 特征和免疫原性与参比产品 Actemra®相似。两组的安全性特征相似，均有轻度至中度不良反应。
该试验在中国临床试验网站（http://www.chinadrugtrials.org.cn/index.html#CTR20190002）注册。
这是首例新型托珠单抗生物类似药 QX003S 的临床报告。本一期随机、对照研究比较了 QX003S 与已批准的托珠单抗产品（Actemra@）的药代动力学、变异性、免疫原性和安全性。结果表明 BAT1806 与参比产品（Actemra@）具有生物等效性，且具有相似的免疫原性、安全性和耐受性特征。
