Paul Strauss Center, Strasbourg, France.
Institut Cancérologie de Strasbourg (ICANS), Strasbourg, France.
PLoS One. 2021 Sep 23;16(9):e0248222. doi: 10.1371/journal.pone.0248222. eCollection 2021.
This first-in-human study was designed to evaluate the pharmacokinetic (PK) equivalence between HD204 and the European Union (EU)-sourced bevacizumab, between HD204 and the United States of America (US)-sourced bevacizumab, and between EU-sourced and US-sourced bevacizumab (NCT03390673).
In this randomized, double-blind, 3-way parallel group, single-dose comparative PK study, healthy male subjects were randomized to receive a single 1 mg/kg intravenous dose of HD204, EU-sourced bevacizumab or US-sourced bevacizumab. PK parameters were calculated using non-compartmental methods. PK equivalence was determined using the pre-defined equivalence margin of 0.8-1.25 in terms of AUC(0-∞) for the pairwise comparisons.
Baseline demographics for the 119 randomized subjects were similar across the three groups. The 90% CIs for the ratio of the geometric means of HD204 to US-sourced bevacizumab, HD204 to EU-sourced bevacizumab, and EU-sourced to US-sourced bevacizumab were all within the interval of 80% to 125% for AUC0-inf, thus demonstrating equivalency in the PK properties for all three treatment groups. Similarly, the ratio of the geometric means for AUC0-last and Cmax were all within the 80% and 125% margins, supporting the robustness of the primary findings. All other PK parameters, including the half-life (t1⁄2) clearance (CL), volume of distribution (Vd) and time of maximum concentration (tmax), were comparable. There was no difference between the 3 treatment arms in terms of vital signs, laboratory tests and adverse events. None of the subjects treated with HD204 had positive ADA results.
HD204 demonstrates equivalent pharmacokinetic profiles compared to those of both US-sourced and EU-sourced bevacizumab. (NCT03390673).
这项首次人体研究旨在评估 HD204 与欧盟（EU）来源贝伐珠单抗、HD204 与美国（US）来源贝伐珠单抗以及 EU 来源与 US 来源贝伐珠单抗之间的药代动力学（PK）等效性（NCT03390673）。
在这项随机、双盲、三向平行组、单次剂量比较 PK 研究中，健康男性受试者被随机分配接受单次 1 mg/kg 静脉注射 HD204、EU 来源贝伐珠单抗或 US 来源贝伐珠单抗。使用非房室方法计算 PK 参数。使用预先定义的等效边界 0.8-1.25 来确定 AUC(0-∞)的成对比较的 PK 等效性。
三组中，119 名随机受试者的基线人口统计学特征相似。HD204 与 US 来源贝伐珠单抗、HD204 与 EU 来源贝伐珠单抗以及 EU 来源与 US 来源贝伐珠单抗的几何均数比值的 90%置信区间均在 80%至 125%范围内，表明所有三组治疗的 PK 特性均等效。同样，AUC0-last 和 Cmax 的几何均数比值均在 80%和 125%范围内，支持主要发现的稳健性。所有其他 PK 参数，包括半衰期（t1⁄2）清除率（CL）、分布容积（Vd）和最大浓度时间（tmax），均相似。在生命体征、实验室检查和不良事件方面，三组治疗之间没有差异。接受 HD204 治疗的受试者均无 ADA 阳性结果。
与 US 来源和 EU 来源的贝伐珠单抗相比，HD204 表现出相当的 PK 特征。（NCT03390673）。
