A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis

The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.

开始日期2020-12-22

申办/合作机构

Ionis Pharmaceuticals, Inc.

NCT03647228 / Completed临床1期

A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis

This Phase 1/2a study is a double-blinded (subject and Investigator), randomized, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple nebulized doses of IONIS-ENaCRx.

开始日期2018-12-13

申办/合作机构

Ionis Pharmaceuticals, Inc.

100 项与 IONIS-ENaCRx 相关的临床结果

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100 项与 IONIS-ENaCRx 相关的转化医学

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100 项与 IONIS-ENaCRx 相关的专利（医药）

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项与 IONIS-ENaCRx 相关的文献（医药）

2024-07-01·ERJ Open Research

Randomised, phase 1/2a trial of ION-827359, an antisense oligonucleotide inhibitor of ENaC

Article

作者: Crosby, Jeff ; Elborn, J Stuart ; Yu, Rosie ; Fischer, Rainald ; Sutharsan, Sivagurunathan ; Guo, Shuling ; Gleiber, Wolfgang ; Horsley, Alex ; Xia, Shuting ; Newman, Kenneth B

BackgroundHyperactivity of epithelial sodium channel (ENaC) with increased sodium absorption is a feature of cystic fibrosis (CF). ION-827359 is a 2.5-generation antisense oligonucleotide targeted to reduce ENaC protein. This study evaluated ION-827359 safety, pharmacokinetics and pharmacodynamics.MethodsIn this three-part phase 1/2a, double-blind, randomised study, healthy volunteers received single doses of placebo or ION-827359 (3, 10, 37.5 or 100 mg; Part 1) or multiple doses of placebo or ION-827359 (5×10 mg, 5×37.5 mg, 5×75 mg or 10×37.5 mg; Part 2). People with CF (pwCF) received multiple doses of placebo or ION-827359 (5×10 mg, 5×37.5 mg, 5×75 mg and 5×100 mg; Part 3). Treatments were administeredviaPari eFlow©mesh nebuliser. The primary outcome was safety; pharmacokinetic and pharmacodynamic parameters were also assessed.Results64 healthy volunteers and 34 pwCF were enrolled. ION-827359 was well tolerated with an acceptable safety profile. There were no clinically relevant changes in laboratory values, ECG or vital signs. Systemic drug exposure was low (plasma half-life ∼2 weeks). Multiple doses of ION-827359 were associated with dose-dependent reductions in ENaC mRNA in bronchial epithelium. After multiple dosing, forced expiratory volume in 1 s was slightly higher in pwCF receiving ION-827359 (+2.9% with ION-827359 100 mgversusplacebo; p=0.27).ConclusionsThe tolerability and safety of ION-827359 appear favourable at this stage of investigation. Reduction in ENaC mRNA supports mechanistic efficacy at the doses and regimens tested, and supports further investigation of ION-827359 in pwCF.

100 项与 IONIS-ENaCRx 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
慢性支气管炎	临床2期	捷克	Ionis Pharmaceuticals, Inc.	2020-12-22
慢性支气管炎	临床2期	匈牙利	Ionis Pharmaceuticals, Inc.	2020-12-22
慢性支气管炎	临床2期	德国	Ionis Pharmaceuticals, Inc.	2020-12-22
慢性支气管炎	临床2期	英国	Ionis Pharmaceuticals, Inc.	2020-12-22
囊性纤维化	临床2期	英国	Ionis Pharmaceuticals, Inc.	2018-12-13
囊性纤维化	临床2期	德国	Ionis Pharmaceuticals, Inc.	2018-12-13

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04441788 (CTgov)	临床2期	慢性支气管炎	60	Placebo (Placebo)	簾願觸鏇蓋網築鏇壓壓(鹹範廠築構襯鏇構簾鑰) = 遞顧製願繭夢鹽顧簾糧範鹹鏇獵製餘艱憲積糧 (鬱遞選鏇廠憲簾夢選淵, 廠遞顧觸積襯艱鹹顧齋 ~ 顧壓衊衊廠獵鹹衊襯築) 更多	-	2022-12-20
				ION-827359 (ION-827359 75 mg)	簾願觸鏇蓋網築鏇壓壓(鹹範廠築構襯鏇構簾鑰) = 淵憲醖鹹願艱積鏇夢憲範鹹鏇獵製餘艱憲積糧 (鬱遞選鏇廠憲簾夢選淵, 網淵艱範夢網夢鹹製獵 ~ 積選淵鏇餘淵選網窪齋) 更多