一项I期随机双盲平行单剂量药代动力学研究，旨在评估KM118（拟用的帕妥珠单抗生物类似药）与参比帕妥珠单抗（Perjeta）在健康男性受试者中的生物相似性。
A phase I, randomized, double-blind, parallel, single-dose pharmacokinetic study to evaluate the biosimilarity of KM118 (proposed pertuzumab biosimilar) with reference pertuzumab (Perjeta) in healthy male subjects.
作者信息
Li Yan, Wang Yu, Yang Caixia, Zhao Na, Wang Xinghe
机构信息
Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, P.R. China.
Beijing SL Pharmaceutical Co., Ltd, Beijing, P.R. China.
出版信息
Ann Med. 2025 Dec;57(1):2523561. doi: 10.1080/07853890.2025.2523561. Epub 2025 Jun 28.
OBJECTIVE
KM118 is a biosimilar to pertuzumab (Perjeta). This study aimed to prove the pharmacokinetics (PK) biosimilarity and evaluate the safety, tolerability, and immunogenicity of KM118 and the original drug Perjeta so that it can be approved for the marketing of biosimilar drugs in China.
METHODS
This was a single-center, randomized, double-blind, two-arm, parallel-group, phase 1 study in healthy male subjects. The sample size was 100 cases. The dosage was 420 mg. Venous blood was collected from the beginning of drug administration to 84 days after drug administration, and the concentration of pertuzumab was determined using ELISA. The primary pharmacokinetic parameter was the area under the concentration-time curve from time zero to the last measurable concentration (AUC) for pertuzumab. If the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the primary parameters fell within the predefined range of 80.00-125.00%, biosimilarity was considered to be established. The safety and immunogenicity were evaluated.
RESULTS
Fifty subjects received 420 mg of intravenous injection of the test (KM118) formulation and 50 subjects received the reference (Perjeta) pertuzumab formulation. The geometric mean of AUC for the test formulation was 74465.82 ± 16308.38 ng·h/mL and for the reference formulation was 69097.83 ± 13278.28 ng·h/mL. The 90% confidence intervals (CIs) for the test/reference ratio for the AUC of pertuzumab ranged from 99.92 to 114.72%, which met the bioequivalence criteria (80.00-125.00%). Similar immunogenicity was observed between Sequences A and B. All of the adverse events (AEs) were Grade 1 or 2, and no SAEs occurred. The test and reference formulations of pertuzumab were well-tolerated by healthy male subjects.
CONCLUSION
Biosimilarity between the test and reference formulations of pertuzumab (KM118 and Perjeta) was demonstrated. Both formulations were well tolerated.
CLINICAL TRIAL REGISTRATION
chinaDrugtrials.org.cn, identifier CTR20202566 (December 17, 2020); chictr.org.cn, identifier ChiCTR2400092982 (November 26, 2024).
目的
KM118是帕妥珠单抗（Perjeta）的生物类似药。本研究旨在证明其药代动力学（PK）生物相似性，并评估KM118与原研药Perjeta的安全性、耐受性和免疫原性，以便其能在中国获批生物类似药上市。
方法
这是一项在健康男性受试者中进行的单中心、随机、双盲、双臂、平行组1期研究。样本量为100例。剂量为420mg。从给药开始至给药后84天采集静脉血，采用酶联免疫吸附测定法（ELISA）测定帕妥珠单抗浓度。主要药代动力学参数是帕妥珠单抗从时间零点至最后可测浓度的浓度-时间曲线下面积（AUC）。如果主要参数的几何平均比（GMR）的90%置信区间（CI）落在预先定义的80.00 - 125.00%范围内，则认为建立了生物相似性。评估安全性和免疫原性。
结果
50名受试者接受420mg静脉注射试验（KM118）制剂，50名受试者接受对照（Perjeta）帕妥珠单抗制剂。试验制剂的AUC几何平均值为74465.82±16308.38ng·h/mL，对照制剂为69097.83±13278.28ng·h/mL。帕妥珠单抗AUC的试验/对照比的90%置信区间为99.92%至114.72%，符合生物等效性标准（80.00 - 125.00%）。序列A和B之间观察到相似的免疫原性。所有不良事件（AE）均为1级或2级，未发生严重不良事件（SAE）。帕妥珠单抗的试验制剂和对照制剂在健康男性受试者中耐受性良好。
结论
证明了帕妥珠单抗（KM118和Perjeta）的试验制剂与对照制剂之间的生物相似性。两种制剂耐受性均良好。
临床试验注册
中国临床试验注册中心，标识符CTR20202566（2020年12月17日）；中国临床试验注册中心，标识符ChiCTR2400092982（2024年11月26日）。
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