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
{"title":"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。","authors":"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","doi":"10.1007/s40259-024-00679-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Nivolumab (Opdivo<sup>®</sup>) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.</p><p><strong>Objectives: </strong>This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo<sup>®</sup>) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed.</p><p><strong>Patients and methods: </strong>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<sub>0-∞</sub>, and the secondary pharmacokinetic endpoints included AUC<sub>0-t</sub> and C<sub>max</sub>. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%.</p><p><strong>Results: </strong>This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo<sup>®</sup> in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo<sup>®</sup> were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC<sub>0-∞</sub>, AUC<sub>0-t</sub>, and C<sub>max</sub> of LY01015 to Opdivo<sup>®</sup> 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.</p><p><strong>Conclusions: </strong>LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles.</p><p><strong>Trial registration: </strong>This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"855-865"},"PeriodicalIF":5.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1007/s40259-024-00679-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Nivolumab (Opdivo<sup>®</sup>) is the first anti-PD-1 antibody approved in the world. LY01015 is a potential biosimilar of nivolumab.</p><p><strong>Objectives: </strong>This phase I study aimed to establish the pharmacokinetic equivalence between LY01015 and the original investigational nivolumab (Opdivo<sup>®</sup>) in healthy Chinese male subjects. Additionally, safety and immunogenicity were assessed.</p><p><strong>Patients and methods: </strong>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<sub>0-∞</sub>, and the secondary pharmacokinetic endpoints included AUC<sub>0-t</sub> and C<sub>max</sub>. Pharmacokinetic bioequivalence was confirmed using standard equivalence margins of 80.00-125.00%.</p><p><strong>Results: </strong>This study is the first to report on the pharmacokinetics, safety, and immunogenicity of Opdivo<sup>®</sup> in healthy individuals. The pharmacokinetics profiles of LY01015 and Opdivo<sup>®</sup> were found to be comparable. The geometric mean ratios (90% confidence intervals) for the AUC<sub>0-∞</sub>, AUC<sub>0-t</sub>, and C<sub>max</sub> of LY01015 to Opdivo<sup>®</sup> 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.</p><p><strong>Conclusions: </strong>LY01015 demonstrated highly similar pharmacokinetics to nivolumab in healthy Chinese male subjects. Both drugs exhibited comparable safety and immunogenicity profiles.</p><p><strong>Trial registration: </strong>This trial is registered at the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/ #ChiCTR2200064771).</p>\",\"PeriodicalId\":9022,\"journal\":{\"name\":\"BioDrugs\",\"volume\":\" \",\"pages\":\"855-865\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BioDrugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40259-024-00679-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioDrugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40259-024-00679-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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 AUC0-∞, and the secondary pharmacokinetic endpoints included AUC0-t and Cmax. 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 AUC0-∞, AUC0-t, and Cmax 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).
期刊介绍：
An essential resource for R&D professionals and clinicians with an interest in biologic therapies.
BioDrugs covers the development and therapeutic application of biotechnology-based pharmaceuticals and diagnostic products for the treatment of human disease.
BioDrugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
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