Table 4.
Clinical trials with experimental compounds targeting ENaC. (https://clinicaltrials.gov/, https://eudract.ema.europa.eu/, accessed on 27 March 2023).
| Test Compound | Study Title/Study Number | Intervention | Trial Phase/ Recruitment Status |
Disease/ Condition |
|---|---|---|---|---|
| ENaC inhibitors | ||||
| VX-371 | Clearing Lungs with ENaC Inhibition in Primary Ciliary Dyskinesia (CLEAN-PCD) NCT02871778 |
VX-371 Hypertonic Saline Placebo VX-371 + HS Ivacaftor | Phase 2 2016–2021 completed |
Primary Ciliary Dyskinesia |
| VX-371 | Safety and Efficacy of VX-371 Solution for Inhalation With and Without Oral Ivacaftor in Subjects With Primary Ciliary Dyskinesia EudraCT2015-004917-26 |
VX-371 (inhalation) Ivacaftor (oral) Placebo |
Phase 2a 2016–2018 completed |
Primary Ciliary Dyskinesia |
| P-1037 | Clearing Lungs With Epithelial Sodium Channel (ENaC) Inhibition in Cystic Fibrosis (CF) (CLEAN-CF) NCT02343445 |
P-1037 Hypertonic Saline Saline | phase 2 2015–2021 completed |
Cystic fibrosis |
| ETD001 | A First in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Inhaled ETD001 NCT04926701 |
inhaled, single dose, and multiple once/twice daily ETD001 Placebo |
Phase 1 2021–2022 completed |
Cystic fibrosis |
| GS-9411 | A Phase 1 Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF) NCT01025713 |
GS-9411 Placebo |
Phase 1 2009–2010 withdrawn |
Cystic fibrosis Mucociliary Clearance |
| GS-9411 | Trial to Assess the Safety, Tolerability and Pharmacokinetics of GS-9411 in Healthy Male Volunteers NCT00800579 | GS-9411 Placebo |
Phase 1 2008–2009 completed |
Cystic fibrosis |
| GS-9411 | A Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS-9411 in Healthy Male Volunteers NCT00951522 |
GS-9411 Placebo |
Phase 1 2009 |
Cystic fibrosis Mucociliary Clearance Airway Hydration |
| AZD5634 | To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration NCT02679729 |
AZD5634 for inhalation AZD5634 for infusion Placebo |
Phase 1 2016 completed |
Cystic fibrosis |
| AZD5634 | A Study to Assess the Effect of AZD5634 on Mucociliary Clearance, Safety, Tolerability and Pharmacokinetic Parameters in Patients With Cystic Fibrosis NCT02950805 |
Placebo AZD5634 |
Phase 1 2017–2018 completed |
Pulmonary/Respiratory Diseases |
| BI 1265162 | A 4-week Study to Test Different Doses of BI 1265162 in Adolescents and Adults With Cystic Fibrosis Using the Respimat® Inhaler NCT04059094 |
BI 1265162 Placebo |
Phase 2 2020 Terminated |
Cystic fibrosis |
| Analogues of SPLUNC1 | ||||
| SPX-101 | A Safety Study of SPX-101 Inhalation Solution in Subjects With Cystic Fibrosis NCT03056989 |
SPX-101 | Phase 1 2017 completed |
Cystic fibrosis |
| SPX-101 | An Efficacy and Safety Study of SPX-101 Inhalation Solution in Subjects With Cystic Fibrosis NCT03229252 |
Placebo SPX-101 |
Phase 2 2017–2019 completed |
Cystic fibrosis |
| Antisense oligonucleotides | ||||
| IONIS-ENaCRx | A Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of IONIS-ENaCRx in Healthy Volunteers and Patients With Cystic Fibrosis NCT 03647228 |
IONIS-ENaCRx Placebo Ascending single and multiple doses inhaled or nebulized |
Phase 1 2018–2020 Completed |
Healthy Subjects Cystic fibrosis |
| ION-827359 Antisense Inhibitor of ENaC (ENaCCRx) |
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 EudraCT2020-000210-15 NCT04441788 |
Placebo ION-827359 Oral inhalation of single-dose once every week up to 13 weeks |
Phase 2a 2020–2021 terminated |
COPD with Chronic Bronchitis |
| Short interfering α-ENaC RNA | ||||
| ARO-ENaC | Study of ARO-ENaC in Healthy Volunteers and in Patients With Cystic Fibrosis NCT04375514 |
ARO-ENaC Placebo | Phase 1 2020–2022 terminated |
Cystic Fibrosis Pulmonary |