{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:52:06Z","timestamp":1783338726149,"version":"3.54.6"},"reference-count":39,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2021,12,18]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal interstitial lung disease (ILD); other ILDs have a progressive, fibrotic phenotype (PF-ILD). Antifibrotic agents can slow but not stop disease progression in patients with IPF or PF-ILD. c-Jun N-terminal kinases (JNKs) are stress-activated protein kinases implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarisation of profibrotic macrophages, fibroblast activation and collagen production. CC-90001, an orally administered (PO), one time per day, JNK inhibitor, is being evaluated in IPF and PF-ILD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a phase 2, randomised, double-blind, placebo-controlled study evaluating efficacy and safety of CC-90001 in patients with IPF (main study) and patients with PF-ILD (substudy). Both include an 8-week screening period, a 24-week treatment period, up to an 80-week active-treatment extension and a 4-week post-treatment follow-up. Patients with IPF (n=165) will be randomised 1:1:1 to receive 200\u2009mg or 400\u2009mg CC-90001 or placebo administered PO one time per day; up to 25 patients\/arm will be permitted concomitant pirfenidone use. Forty-five patients in the PF-ILD substudy will be randomised 2:1 to receive 400\u2009mg CC-90001 or placebo. The primary endpoint is change in per cent predicted forced vital capacity from baseline to Week 24 in patients with IPF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>This study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03142191\">NCT03142191<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjresp-2021-001060","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T10:43:23Z","timestamp":1642675403000},"page":"e001060","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct03142191","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Zoran","family":"Popmihajlov","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna J","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S","family":"Horan","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atalanta","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Radiology, National Jewish Health, Denver, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W","family":"Noble","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Richeldi","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli IRCSS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore F","family":"Reiss","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, New Jersey, USA"},{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"2025083110262820000_9.1.e001060.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705751"},{"key":"2025083110262820000_9.1.e001060.2","doi-asserted-by":"crossref","DOI":"10.1186\/s12931-019-1271-z","article-title":"The European MultiPartner IPF registry (EMPIRE): validating long-term prognostic factors in idiopathic pulmonary fibrosis","volume":"21","author":"Tran","year":"2020","journal-title":"Respir Res"},{"key":"2025083110262820000_9.1.e001060.3","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-2572"},{"key":"2025083110262820000_9.1.e001060.4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S2213-2600(17)30433-2","article-title":"Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society white paper","volume":"6","author":"Lynch","year":"2018","journal-title":"Lancet Respir Med"},{"key":"2025083110262820000_9.1.e001060.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402582"},{"key":"2025083110262820000_9.1.e001060.6","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00026-2015"},{"key":"2025083110262820000_9.1.e001060.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402584"},{"key":"2025083110262820000_9.1.e001060.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60405-4"},{"key":"2025083110262820000_9.1.e001060.9","unstructured":"ESBRIET (pirfenidone) [package insert]. South San Francisco, CA: Genentech, Inc; 2019."},{"key":"2025083110262820000_9.1.e001060.10","unstructured":"OFEV (nintedanib) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2020."},{"key":"2025083110262820000_9.1.e001060.11","unstructured":"OFEV (nintedanib) [summary of product characteristics]. Ingelheim am Rhein, Germany: Boehringer Ingelheim International GmbH; 2019."},{"key":"2025083110262820000_9.1.e001060.12","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/resp.13024","article-title":"Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: tolerability and adverse drug reactions","volume":"22","author":"Galli","year":"2017","journal-title":"Respirology"},{"key":"2025083110262820000_9.1.e001060.13","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0076-2018","article-title":"Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases","volume":"27","author":"Cottin","year":"2018","journal-title":"Eur Respir Rev"},{"key":"2025083110262820000_9.1.e001060.14","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1080\/03007995.2019.1647040","article-title":"Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management","volume":"35","author":"Wijsenbeek","year":"2019","journal-title":"Curr Med Res Opin"},{"key":"2025083110262820000_9.1.e001060.15","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2017-000212"},{"key":"2025083110262820000_9.1.e001060.16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S2213-2600(19)30341-8","article-title":"Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial","volume":"8","author":"Maher","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025083110262820000_9.1.e001060.17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908681"},{"key":"2025083110262820000_9.1.e001060.18","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0174OC"},{"key":"2025083110262820000_9.1.e001060.19","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.06.00012106"},{"key":"2025083110262820000_9.1.e001060.20","doi-asserted-by":"publisher","DOI":"10.1002\/path.1208"},{"key":"2025083110262820000_9.1.e001060.21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0226904","article-title":"Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models","volume":"15","author":"van der Velden","year":"2020","journal-title":"PLoS One"},{"key":"2025083110262820000_9.1.e001060.22","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00043-14"},{"key":"2025083110262820000_9.1.e001060.23","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00340.2004"},{"key":"2025083110262820000_9.1.e001060.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.07.016"},{"key":"2025083110262820000_9.1.e001060.25","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.09.015"},{"key":"2025083110262820000_9.1.e001060.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.12.027"},{"key":"2025083110262820000_9.1.e001060.27","doi-asserted-by":"crossref","DOI":"10.1186\/s40169-016-0117-2","article-title":"JNK inhibition reduces lung remodeling and pulmonary fibrotic systemic markers","volume":"5","author":"van der Velden","year":"2016","journal-title":"Clin Transl Med"},{"key":"2025083110262820000_9.1.e001060.28","unstructured":"Bennett B , Blease K , Ye Y . CC-90001, a second generation Jun N-terminal kinase (JNK) inhibitor for the treatment of idiopathic pulmonary fibrosis. C38 understanding therapeutics in IPF, 2017: A5409."},{"key":"2025083110262820000_9.1.e001060.29","doi-asserted-by":"crossref","first-page":"18193","DOI":"10.1021\/acs.jmedchem.1c01716","article-title":"Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001","volume":"64","author":"Nagy","year":"2021","journal-title":"J Med Chem"},{"key":"2025083110262820000_9.1.e001060.30","article-title":"Evaluation of the JNK inhibitor, CC-90001, in a phase 1B pulmonary fibrosis trial","volume":"50","author":"Greenberg","year":"2017","journal-title":"Eur Respir J"},{"key":"2025083110262820000_9.1.e001060.31","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1148\/radiol.2017161177","article-title":"Idiopathic pulmonary fibrosis: data-driven textural analysis of extent of fibrosis at baseline and 15-month follow-up","volume":"285","author":"Humphries","year":"2017","journal-title":"Radiology"},{"key":"2025083110262820000_9.1.e001060.32","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01384-2018"},{"key":"2025083110262820000_9.1.e001060.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2009.09.006"},{"key":"2025083110262820000_9.1.e001060.34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5539\/gjhs.v5n6p131","article-title":"Content validity of CASA-Q cough domains and UCSD-SOBQ for use in patients with idiopathic pulmonary fibrosis","volume":"5","author":"Gries","year":"2013","journal-title":"Glob J Health Sci"},{"key":"2025083110262820000_9.1.e001060.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050093"},{"key":"2025083110262820000_9.1.e001060.36","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.119974"},{"key":"2025083110262820000_9.1.e001060.37","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00081102"},{"key":"2025083110262820000_9.1.e001060.38","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2466-14-120"},{"key":"2025083110262820000_9.1.e001060.39","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.2214\/AJR.17.18947","article-title":"CT-Pathologic correlation of major types of pulmonary fibrosis: insights for revisions to current guidelines","volume":"210","author":"Chung","year":"2018","journal-title":"AJR Am J Roentgenol"}],"container-title":["BMJ Open Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjresp-2021-001060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T17:26:34Z","timestamp":1756661194000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopenrespres.bmj.com\/lookup\/doi\/10.1136\/bmjresp-2021-001060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,20]]},"published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1136\/bmjresp-2021-001060"],"URL":"https:\/\/doi.org\/10.1136\/bmjresp-2021-001060","relation":{},"ISSN":["2052-4439"],"issn-type":[{"value":"2052-4439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]}}}