Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial.

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Xin Huang, Xiang Hong, Shuang Yang, Ling Ye, Xiaoyan Yang, Chang Cui, Qian Wu, Wei Wang, Jie Huang, Guoping Yang
{"title":"Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial.","authors":"Xin Huang, Xiang Hong, Shuang Yang, Ling Ye, Xiaoyan Yang, Chang Cui, Qian Wu, Wei Wang, Jie Huang, Guoping Yang","doi":"10.1080/13543784.2024.2443756","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers.</p><p><strong>Methods: </strong>Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603. Follow-up was 12 weeks. Adverse event (AE) profiles, vital signs, and blood samples were collected for assessment of safety, PK, and expression of type I interferon inducible genes.</p><p><strong>Results: </strong>Of the 46 subjects, 44 completed treatment. In the experimental group of 34 subjects (mean age 26.6 years), 30 experienced treatment-emergent adverse events (TEAEs), with a total of 102 occurrences, resulting in an incidence rate of 88.2%. The most commonly reported drug-related AEs were upper respiratory tract infection (17.6%), all of which were ≤ grade 2. GR1603 exhibits non-linear PK in the dose range of 0.1 mg/kg to 9 mg/kg. All samples were negative for anti-drug antibodies before and after dosing. The degrees of IFN gene signature were significantly inhibited in the higher dose groups.</p><p><strong>Conclusion: </strong>The safety/tolerability, PK and exploratory metrics observed in this study support further clinical development of GR1603.</p><p><strong>Clinical trial registration: </strong>www.chictr.org.cn/searchproj.html identifier is ChiCTR2100045628.</p>","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-7"},"PeriodicalIF":4.9000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on investigational drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13543784.2024.2443756","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers.

Methods: Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603. Follow-up was 12 weeks. Adverse event (AE) profiles, vital signs, and blood samples were collected for assessment of safety, PK, and expression of type I interferon inducible genes.

Results: Of the 46 subjects, 44 completed treatment. In the experimental group of 34 subjects (mean age 26.6 years), 30 experienced treatment-emergent adverse events (TEAEs), with a total of 102 occurrences, resulting in an incidence rate of 88.2%. The most commonly reported drug-related AEs were upper respiratory tract infection (17.6%), all of which were ≤ grade 2. GR1603 exhibits non-linear PK in the dose range of 0.1 mg/kg to 9 mg/kg. All samples were negative for anti-drug antibodies before and after dosing. The degrees of IFN gene signature were significantly inhibited in the higher dose groups.

Conclusion: The safety/tolerability, PK and exploratory metrics observed in this study support further clinical development of GR1603.

Clinical trial registration: www.chictr.org.cn/searchproj.html identifier is ChiCTR2100045628.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信