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.

Start Date22 Dec 2020

Sponsor / Collaborator

Ionis Pharmaceuticals, Inc.

NCT03647228 / CompletedPhase 1

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.

Start Date13 Dec 2018

Sponsor / Collaborator

Ionis Pharmaceuticals, Inc.

100 Clinical Results associated with IONIS-ENaCRx

100 Translational Medicine associated with IONIS-ENaCRx

100 Patents (Medical) associated with IONIS-ENaCRx

Literatures (Medical) associated with IONIS-ENaCRx

01 Jul 2024·ERJ Open Research

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

Article

Author: Crosby, Jeff ; Yu, Rosie ; Elborn, J Stuart ; Fischer, Rainald ; Guo, Shuling ; Sutharsan, Sivagurunathan ; 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 Deals associated with IONIS-ENaCRx

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Bronchitis, Chronic	Phase 2	CZ	Ionis Pharmaceuticals, Inc.	22 Dec 2020
Bronchitis, Chronic	Phase 2	HU	Ionis Pharmaceuticals, Inc.	22 Dec 2020
Bronchitis, Chronic	Phase 2	DE	Ionis Pharmaceuticals, Inc.	22 Dec 2020
Bronchitis, Chronic	Phase 2	GB	Ionis Pharmaceuticals, Inc.	22 Dec 2020
Cystic Fibrosis	Phase 2	GB	Ionis Pharmaceuticals, Inc.	13 Dec 2018
Cystic Fibrosis	Phase 2	DE	Ionis Pharmaceuticals, Inc.	13 Dec 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04441788 (CTgov)	Phase 2	Bronchitis, Chronic	60	Placebo (Placebo)	gedhbtzgdk(acfwrjeztu) = lrofsbmccv zjbxrsqqhr (nsufnyhjjb, lxfuuypvjq - nukuikbojt) View more	-	20 Dec 2022
				ION-827359 (ION-827359 75 mg)	gedhbtzgdk(acfwrjeztu) = cgixqngtif zjbxrsqqhr (nsufnyhjjb, ujmwxwmlve - rbrssbtveh) View more

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