{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:44Z","timestamp":1785430484612,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF21OC0071860"],"award-info":[{"award-number":["NNF21OC0071860"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NNF21OC0071860"],"award-info":[{"award-number":["NNF21OC0071860"]}],"id":[{"id":"https:\/\/ror.org\/04txyc737","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (F-ILD) are characterised by progressive loss of lung function, worsening symptoms, and poor prognosis. Current antifibrotic therapies slow disease progression but do not arrest or reverse fibrosis and are frequently associated with adverse effects. Senicapoc, a selective KCa3.1 channel inhibitor, has shown antifibrotic effects in preclinical models, human lung myofibroblasts, and ex vivo human lung tissue. This study aims to determine whether senicapoc reduces the rate of decline in forced vital capacity (FVC) over 26 weeks, compared with placebo, in patients with IPF or other progressive F-ILD, while also characterising safety and tolerability. Methods: This is an investigator-initiated, prospective, randomised, double-blind, placebo-controlled, multicentre phase II trial. Adults with IPF or other F-ILD with documented progression despite optimised antifibrotic management according to standard care and individual tolerability will be randomised 1:1 to receive senicapoc 30 mg once daily or a matching placebo for 26 weeks in addition to standard care. The primary outcome is the rate of decline in FVC over 26 weeks. Secondary outcomes include changes in diffusion capacity, 6 min walk distance, dyspnoea, health-related quality of life, adverse events, and senicapoc plasma concentrations, with mortality and exacerbations assessed as exploratory outcomes. The planned sample size is 140 participants. The primary analysis will be conducted in the intention-to-treat population using a linear mixed-effects model for repeated measurements. Results: No results are available, as this article describes the study protocol. Conclusions: This study will provide proof of concept for the efficacy, safety, and tolerability of senicapoc in progressive fibrotic interstitial lung disease. If successful, it will support further clinical development of KCa3.1 inhibition as a novel antifibrotic strategy.<\/jats:p>","DOI":"10.3390\/diagnostics16111649","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:00:36Z","timestamp":1779955236000},"page":"1649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Senicapoc in Patients with Idiopathic Pulmonary Fibrosis or Other Progressive Fibrotic Interstitial Lung Diseases: Protocol for a Randomised, Double-Blind, Placebo-Controlled, Multicentre Phase II Trial"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3022-7105","authenticated-orcid":false,"given":"Line","family":"K\u00f8lner-Augustson","sequence":"first","affiliation":[{"name":"Department of Medicine, Lillebaelt Hospital, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7798-9871","authenticated-orcid":false,"given":"Alan","family":"Altraja","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Lung Clinic, Tartu University Hospital, 50411 Tartu, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Bendstrup","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases and Allergy, Aarhus University Hospital, 5200 Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bradding","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester Respiratory NIHR BRC, Glenfield Hospital, Leicester LE1 7RH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9794-0829","authenticated-orcid":false,"given":"Nanna","family":"Makholm","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases and Allergy, Aarhus University Hospital, 5200 Aarhus N, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-7666","authenticated-orcid":false,"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 5000 Aarhus C, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-3463","authenticated-orcid":false,"given":"Ole","family":"Hilberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lillebaelt Hospital, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS\/ERS\/JRS\/ALAT Clinical Practice Guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2000085","DOI":"10.1183\/13993003.00085-2020","article-title":"The natural history of progressive fibrosing interstitial lung diseases","volume":"55","author":"Brown","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMra2005230","article-title":"Spectrum of Fibrotic Lung Diseases","volume":"383","author":"Wijsenbeek","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1002\/mco2.744","article-title":"Pulmonary fibrosis: Pathogenesis and therapeutic strategies","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","article-title":"Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis","volume":"370","author":"Richeldi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","article-title":"A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis","volume":"370","author":"King","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1056\/NEJMoa2503643","article-title":"Nerandomilast in Patients with Progressive Pulmonary Fibrosis","volume":"392","author":"Maher","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1056\/NEJMoa2414108","article-title":"Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis","volume":"392","author":"Richeldi","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2004587","DOI":"10.1183\/13993003.04587-2020","article-title":"Effects of nintedanib by inclusion criteria for progression of interstitial lung disease","volume":"59","author":"Maher","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1056\/NEJMoa1908681","article-title":"Nintedanib in Progressive Fibrosing Interstitial Lung Diseases","volume":"381","author":"Flaherty","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S2213-2600(20)30554-3","article-title":"Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): A double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Behr","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1124\/mol.116.108068","article-title":"Structural Insights into the Atomistic Mechanisms of Action of Small Molecule Inhibitors Targeting the KCa3.1 Channel Pore","volume":"91","author":"Nguyen","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1586\/ecp.10.11","article-title":"Therapeutic potential of KCa3.1 blockers: Recent advances and promising trends","volume":"3","author":"Wulff","year":"2010","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116573","DOI":"10.1016\/j.bcp.2024.116573","article-title":"Intermediate conductance calcium-activated potassium channel (KCa3.1) in cancer: Emerging roles and therapeutic potentials","volume":"230","year":"2024","journal-title":"Biochem Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1592\/phco.26.11.1557","article-title":"Dose-Escalation Study of ICA-17043 in Patients with Sickle Cell Disease","volume":"26","author":"Ataga","year":"2006","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-pathmechdis-012418-012838","article-title":"Pathophysiology of Sickle Cell Disease","volume":"14","author":"Sundd","year":"2019","journal-title":"Annu. Rev. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1365-2141.2010.08520.x","article-title":"Improvements in haemolysis and indicators of erythrocyte survival do not correlate with acute vaso-occlusive crises in patients with sickle cell disease: A phase III randomized, placebo-controlled, double-blind study of the Gardos channel blocker senicapoc (ICA-17043)","volume":"153","author":"Ataga","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Roach, K.M., Duffy, S.M., Coward, W., Feghali-Bostwick, C., Wulff, H., and Bradding, P. (2013). The K+ Channel KCa3.1 as a Novel Target for Idiopathic Pulmonary Fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0085244"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13069-015-0022-0","article-title":"Human lung myofibroblast TGF\u03b21-dependent Smad2\/3 signalling is Ca2+-dependent and regulated by KCa3.1 K+ channels","volume":"8","author":"Roach","year":"2015","journal-title":"Fibrogenesis Tissue Repair."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12931-014-0155-5","article-title":"Increased constitutive \u03b1SMA and Smad2\/3 expression in idiopathic pulmonary fibrosis myofibroblasts is KCa3.1-dependent","volume":"15","author":"Roach","year":"2014","journal-title":"Respir. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41598-017-18555-9","article-title":"A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis","volume":"8","author":"Roach","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/bph.14939","article-title":"Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases","volume":"177","author":"Roach","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1165\/rcmb.2016-0092OC","article-title":"Inhibition of the KCa3.1 Channel Alleviates Established Pulmonary Fibrosis in a Large Animal Model","volume":"56","author":"Organ","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19893","DOI":"10.1038\/s41598-019-56412-z","article-title":"KCa3.1 channel blockade attenuates microvascular remodelling in a large animal model of bleomycin-induced pulmonary fibrosis","volume":"9","author":"Derseh","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","first-page":"6683195","article-title":"Increased Levels of ER Stress and Apoptosis in a Sheep Model for Pulmonary Fibrosis Are Alleviated by In Vivo Blockade of the KCa3.1 Ion Channel","volume":"2021","author":"Perera","year":"2021","journal-title":"Can. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14518","DOI":"10.1073\/pnas.0903458106","article-title":"Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels","volume":"106","author":"Grgic","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.toxlet.2018.07.020","article-title":"The KCa3.1 blocker TRAM-34 inhibits proliferation of fibroblasts in paraquat-induced pulmonary fibrosis","volume":"295","author":"Xie","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177461","DOI":"10.1016\/j.ejphar.2025.177461","article-title":"TGF\u03b21 generates a pro-fibrotic proteome in human lung parenchyma that is sensitive to pharmacological intervention","volume":"997","author":"Maxwell","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Roach, K.M., Castells, E., Dixon, K., Mason, S., Elliott, G., Marshall, H., Poblocka, M.A., Macip, S., Richardson, M., and Khalfaoui, L. (2021). Evaluation of Pirfenidone and Nintedanib in a Human Lung Model of Fibrogenesis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.679388"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/aas.14072","article-title":"Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial","volume":"66","author":"Granfeldt","year":"2022","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1182\/blood-2007-08-110098","article-title":"Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia","volume":"111","author":"Ataga","year":"2008","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"EuroQol Group (1990). EuroQol\u2014A new facility for the measurement of health-related quality of life. Health Policy, 16, 199\u2013208.","DOI":"10.1016\/0168-8510(90)90421-9"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1136\/thx.2010.139121","article-title":"Development and validity testing of an IPF-specific version of the St George\u2019s Respiratory Questionnaire","volume":"65","author":"Yorke","year":"2010","journal-title":"Thorax"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/thoraxjnl-2012-201581","article-title":"The development and validation of the King\u2019s Brief Interstitial Lung Disease (K-BILD) health status questionnaire","volume":"67","author":"Patel","year":"2012","journal-title":"Thorax"},{"key":"ref_35","unstructured":"(2026, April 24). CTEP Trial Development and Conduct\u2014NCI, Available online: https:\/\/dctd.cancer.gov\/research\/ctep-trials\/trial-development."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"00591","DOI":"10.1183\/23120541.00591-2021","article-title":"Mortality and survival in idiopathic pulmonary fibrosis: A systematic review and meta-analysis","volume":"8","author":"Zheng","year":"2022","journal-title":"ERJ Open Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/11\/1649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:17:33Z","timestamp":1779956253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/11\/1649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":36,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["diagnostics16111649"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16111649","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}