Pharmacokinetics, Safety, and Immunogenicity of a Biosimilar of Nivolumab (LY01015): A Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Trial in Healthy Chinese Male Subjects.

IF 5.4 2区医学 Q1 IMMUNOLOGY

BioDrugs Pub Date : 2024-11-01 Epub Date: 2024-09-24 DOI:10.1007/s40259-024-00679-w

Wei Wang, Shengnan Zhang, Changlin Dou, Baihui Hu, Hongtao Song, Fan Qi, Yanyan Zhao, Xiaojing Li, Ming Zhou, Jinlian Xie, Kunhong Deng, Qian Wu, Ling Ye, Chang Cui, Li Liu, Jie Huang, Guoping Yang

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引用次数: 0

Abstract

Background: Nivolumab (Opdivo^®) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.

Objectives: This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo^®) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed.

Patients and methods: A randomized, double-blind, parallel-controlled, phase I trial was conducted with 176 healthy male adults receiving a single intravenous infusion of LY01015 or nivolumab at 0.3 mg/kg. Pharmacokinetics, safety, and immunogenicity were evaluated over a 99-day period. The primary pharmacokinetics endpoint was AUC_0-∞, and the secondary pharmacokinetic endpoints included AUC_0-t and C_max. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%.

Results: This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo^® in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo^® were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC_0-∞, AUC_0-t, and C_max of LY01015 to Opdivo^® were 94.49% (90.29-98.88%), 94.92% (88.73-101.54%), and 96.55% (93.32-99.90%), respectively, falling within the conventional bioequivalence criteria of 80.00-125.00%. The safety and immunogenicity were also comparable between the two groups.

Conclusions: LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles.

Trial registration: This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).

查看原文本刊更多论文

Nivolumab（LY01015）生物仿制药的药代动力学、安全性和免疫原性：一项针对中国男性健康受试者的随机、双盲、平行对照 I 期临床试验。

背景Nivolumab (Opdivo®) 是全球首个获批的抗 PD-1 抗体。LY01015是Nivolumab的潜在生物类似药：本 I 期研究旨在确定 LY01015 与原研药 nivolumab (Opdivo®) 在中国男性健康受试者中的药代动力学等效性。此外，还评估了安全性和免疫原性：我们对176名健康男性成年人进行了一项随机、双盲、平行对照的I期试验，他们接受了单次静脉输注LY01015或0.3 mg/kg的nivolumab。在 99 天的时间里对药代动力学、安全性和免疫原性进行了评估。主要药代动力学终点是AUC0-∞，次要药代动力学终点包括AUC0-t和Cmax。药代动力学生物等效性采用 80.00-125.00% 的标准等效比值进行确认：该研究首次报告了Opdivo®在健康人体内的药代动力学、安全性和免疫原性。研究发现，LY01015和Opdivo®的药代动力学特征相当。LY01015与Opdivo®的AUC0-∞、AUC0-t和Cmax的几何平均比（90%置信区间）分别为94.49%（90.29-98.88%）、94.92%（88.73-101.54%）和96.55%（93.32-99.90%），符合80.00-125.00%的常规生物等效性标准。两组的安全性和免疫原性也相当：结论：在中国男性健康受试者中，LY01015与nivolumab的药代动力学高度相似。结论：在中国男性健康受试者中，LY01015与nivolumab的药代动力学非常相似，两种药物的安全性和免疫原性也相当：本试验已在中国临床试验注册中心网站注册 ( https://www.chictr.org.cn/ #ChiCTR2200064771)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BioDrugs 医学-免疫学

CiteScore

12.60

自引率

2.90%

发文量

审稿时长

>12 weeks

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