抗微生物 RNA-328 眼科溶液 SHJ002 在儿科受试者中的安全性和耐受性:首次人体临床研究。

IF 3.2 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Jiunn-Liang Chen MD , Wei-Yu Lai MD , Reuy-Tay Lin MD , Suh-Hang H. Juo MD, PhD , Chung-Ling Liang MD, PhD
{"title":"抗微生物 RNA-328 眼科溶液 SHJ002 在儿科受试者中的安全性和耐受性:首次人体临床研究。","authors":"Jiunn-Liang Chen MD ,&nbsp;Wei-Yu Lai MD ,&nbsp;Reuy-Tay Lin MD ,&nbsp;Suh-Hang H. Juo MD, PhD ,&nbsp;Chung-Ling Liang MD, PhD","doi":"10.1016/j.clinthera.2024.08.015","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.</div></div><div><h3>Methods</h3><div>This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability.</div></div><div><h3>Findings</h3><div>There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as “unrelated to study drug.”</div></div><div><h3>Implications</h3><div>SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. ClinicalTrials.gov identifier: NCT04928144.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 10","pages":"Pages 768-772"},"PeriodicalIF":3.2000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and Tolerability of Anti–microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study\",\"authors\":\"Jiunn-Liang Chen MD ,&nbsp;Wei-Yu Lai MD ,&nbsp;Reuy-Tay Lin MD ,&nbsp;Suh-Hang H. Juo MD, PhD ,&nbsp;Chung-Ling Liang MD, PhD\",\"doi\":\"10.1016/j.clinthera.2024.08.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.</div></div><div><h3>Methods</h3><div>This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability.</div></div><div><h3>Findings</h3><div>There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as “unrelated to study drug.”</div></div><div><h3>Implications</h3><div>SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. ClinicalTrials.gov identifier: NCT04928144.</div></div>\",\"PeriodicalId\":10699,\"journal\":{\"name\":\"Clinical therapeutics\",\"volume\":\"46 10\",\"pages\":\"Pages 768-772\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0149291824002388\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0149291824002388","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

目的:据报道,microRNA-328 是近视发生的一个风险因素。SHJ002是microRNA-328的反义词,SHJ002被配制成眼药水,用于新型microRNA疗法。我们旨在研究 SHJ002 眼科溶液在儿童中的安全性和耐受性:这是一项在健康儿童中进行的单中心、开放标签、首次人体试验(NCT04928144)。所有受试者都接受了研究药物。试验分为两个阶段。第一阶段为受试者内部剂量递增研究,第二阶段为最高耐受剂量研究。每名受试者随机选择一只眼作为研究对象,将SHJ002眼药水注入其中,另一只未经治疗的眼作为阴性对照。3 名参与者被分配到第 1 阶段,他们接受了 3 种浓度(0.025%、0.08% 和 0.25%)的眼药水,每种浓度的眼药水连续使用 3 天。第 2 阶段使用第 1 阶段的最高耐受剂量,招募另外 9 名参与者进行为期 28 天的治疗。对眼部评估、体格检查和生命体征进行测量,以评估安全性和耐受性:共有 4 名男孩和 8 名女孩,平均年龄为 12.3 岁,标准差为 1.56。所有参与者均为亚洲人。第一阶段使用的三种浓度均耐受良好,第二阶段使用的剂量为 0.25%。没有不适报告。仅有1名参与者未接受治疗的眼睛出现轻微不良反应(点状角膜炎),但被认为 "与研究药物无关":SHJ002是一种新型microRNA疗法,采用滴眼疗法。SHJ002眼药水总体上是安全和耐受的,值得在II期和III期试验中进一步研究:NCT04928144。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and Tolerability of Anti–microRNA-328 Ophthalmic Solution, SHJ002, in Pediatric Subjects: First-in-Human Clinical Study

Purpose

microRNA-328 has been reported as a risk factor for myopia development. SHJ002 is an antisense for microRNA-328, and SHJ002 was formulated as ophthalmic solution for a novel microRNA therapy. We aimed to investigate the safety and tolerability of SHJ002 ophthalmic solution in children.

Methods

This was a single-center, open-label, first-in-human trial in healthy children (NCT04928144). All subjects received the study medication. The trial had 2 stages. Stage 1 was an intrasubject dose-escalation study, and stage 2 was the highest tolerable dose study. The SHJ002 ophthalmic solution was instilled in a randomly selected study eye in each participant, whereas the other untreated eye served as a negative control. Three participants were assigned to stage 1, and they received eye drops of 3 concentrations (0.025%, 0.08%, and 0.25%), each of which was used for 3 consecutive days. The highest tolerable dose from stage 1 was used in stage 2 where another 9 participants were recruited for 28-day treatment. Ocular assessments, physical examination, and vital signs were measured to evaluate safety and tolerability.

Findings

There were 4 boys and 8 girls with a mean age of 12.3 years and a SD of 1.56. All participants were Asians. All 3 concentrations used in stage 1 were well tolerated, and the dose of 0.25% was used in stage 2. There were no reports of discomfort. There was only 1 mild adverse event (punctate keratitis) in the untreated eye in 1 participant, which was deemed as “unrelated to study drug.”

Implications

SHJ002 is a novel microRNA therapy that uses eye drop instillation. SHJ002 ophthalmic solution is generally safe and tolerable, which warrants further investigations in Phase II and III trials. ClinicalTrials.gov identifier: NCT04928144.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Clinical therapeutics
Clinical therapeutics 医学-药学
CiteScore
6.00
自引率
3.10%
发文量
154
审稿时长
9 weeks
期刊介绍: Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.
×
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