A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Yu Zhu, Chen Li, Liming Chen, Haiyan Liu, Lun Ou, Tong Li, Xuan Wang, Tenghua Wang, Jingyuan Tian, Xintong Liang, Zhiqin Hu, Yaoxuan Zhan, Shuangshuang Xiao, Xiaole Wang, Yongmei Li, Jin He, Qingshan Zheng, Haifeng Song, Xianbo Li, Yi Fang
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引用次数: 0

Abstract

Background and objective: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®).

Methods: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated.

Results: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA).

Conclusion: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

比较 GB221 注射液和曲妥珠单抗(赫赛汀®)在中国健康成人中的药代动力学、安全性和免疫原性的 I 期临床研究。
背景和目的:GB221 是一种重组人源化抗 HER2 单克隆抗体。本研究旨在评估 GB221 在中国健康成人中与曲妥珠单抗(赫赛汀®)相比的药代动力学、安全性和免疫原性:在这项随机、双盲、平行分组的 I 期临床试验中,88 名受试者按 1:1 随机分配,接受 GB221 或曲妥珠单抗(6 毫克/千克)单次静脉输注(90-100 分钟)。对GB221和曲妥珠单抗的主要药代动力学参数--最大观察血清浓度(Cmax)、从零到t时最后一个可定量浓度的血清浓度-时间曲线下面积(AUC0-t)和从零到无穷大的血清浓度-时间曲线下面积(AUC0-∞)--进行比较,以确定90%置信区间(CI)是否达到80%-125%的生物等效性标准。此外,还对安全性和免疫原性进行了评估:GB221组(43人)和曲妥珠单抗组(44人)显示出相似的药代动力学特征。两组的Cmax、AUC0-t和AUC0-∞的几何平均比(90% CI)分别为107.53%(102.25-113.07%)、108.31%(103.57-113.26%)和108.34%(103.57-113.33%)。GB221组和曲妥珠单抗组的治疗突发不良事件(TEAEs)发生率分别为83.7%(36/43)和95.5%(42/44)。没有受试者因TEAEs退出试验,也没有发生严重不良事件。所有受试者的抗药抗体(ADA)检测结果均为阴性:GB221在中国健康成人中的药代动力学与曲妥珠单抗相似,安全性和免疫原性相当。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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