{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:27:29Z","timestamp":1772166449033,"version":"3.50.1"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000996","name":"Department of Foreign Affairs and Trade, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1129600"],"award-info":[{"award-number":["OPP1129600"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020171","name":"Foreign, Commonwealth and Development Office","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009099","name":"Irish Aid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In 2023, tuberculosis (TB) returned to being the world\u2019s leading cause of death from a single infectious agent. Current standard of care for drug-sensitive tuberculosis (DS-TB) treatment has a long duration with risk of poor compliance and outcomes and increased risk of development of resistant strains. Sorfequiline (S) is a second-generation diarylquinoline with the potential to contribute both to increased efficacy and improved safety and to a shorter TB treatment regimen for both DS-TB and drug-resistant DR-TB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>NC-009 is a phase 2, multicentre, partially blinded, randomized clinical trial conducted in five treatment arms, including three doses of sorfequiline in combination with pretomanid and linezolid for 8 weeks followed by 7 or 18 weeks of HR depending on the participant meeting criteria to stop treatment at week 15. There is also a BPaL arm and standard of care arm, both for a 26-week treatment duration. The study population is smear-positive, DS-TB. The primary objective of the study is to determine the optimal dose of sorfequiline to move forward to a potential phase 3 study based on efficacy and safety data. The study is being conducted in Georgia, South Africa, Tanzania, Uganda, and the Philippines in accordance with ICH-GCP and after approval of all relevant country health authorities and ethics committees.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>NC-009 is a first in-patient, dose-ranging, phase 2 trial of sorfequiline, with an innovative design combining ph2a, ph2b, and ph2c elements that simultaneously allow for dose selection, preliminary evaluation of treatment duration, robust collection of safety data, evaluation of drug-drug interaction with antiretroviral medications, and pharmacokinetic assessment of study drugs. The study is currently ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number {4}<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT 06058299. Registered on 09 September 2023.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-025-09413-5","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:45:19Z","timestamp":1767707119000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protocol for a phase 2, partially blinded, randomized trial assessing the safety and efficacy of sorfequiline or bedaquiline in combination with pretomanid and linezolid in adult participants with newly diagnosed, drug-sensitive, smear-positive pulmonary tuberculosis (NC-009)"],"prefix":"10.1186","volume":"27","author":[{"given":"M.","family":"Olugbosi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Beumont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Lombard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Nedelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Timm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Black","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Bruning-Barry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Betteridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Egizi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Marcopulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Seidel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Foraida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Benhayoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"9413_CR1","unstructured":"WHO. Global tuberculosis report. Geneva: World Health Organization; 2024. Report No.: ISBN 978\u201392\u20134\u2013010154\u20138."},{"key":"9413_CR2","unstructured":"WHO. WHO operational handbook on tuberculosis. Worlsd Health Organization; 2022. Contract No.: ISBN: 978\u201392\u20134\u2013006312\u20139."},{"key":"9413_CR3","unstructured":"WHO. Rapid communication on updated guidance on the management of TB in children and adolescents. 2021."},{"issue":"24","key":"9413_CR4","first-page":"2377","volume":"382","author":"F Conradie","year":"2020","unstructured":"Conradie F, Everitt D, Crook AM. Treatment of highly drug-resistant pulmonary tuberculosis. Reply. N Engl J Med. 2020;382(24):2377.","journal-title":"N Engl J Med"},{"issue":"9","key":"9413_CR5","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1056\/NEJMoa2119430","volume":"387","author":"F Conradie","year":"2022","unstructured":"Conradie F, Bagdasaryan TR, Borisov S, Howell P, Mikiashvili L, Ngubane N, et al. Bedaquiline-pretomanid-linezolid regimens for drug-resistant tuberculosis. N Engl J Med. 2022;387(9):810\u201323.","journal-title":"N Engl J Med"},{"key":"9413_CR6","unstructured":"WHO. Rapid communication: key changes to the treatment of drug-resistant tuberculosis. online: World Health Organization; 2022 May 2022. Report No.: WHO Reference Number: WHO\/UCN\/TB\/2022.2."},{"key":"9413_CR7","doi-asserted-by":"crossref","unstructured":"Tanseen R B, F, Tyagi S, Li, D, Williams K, Converse P, Dartois V, Yang, T, Mendel C, Midliuli K, Nuermberger E. Contribution of oxazolidinones to efficacy of novel regimens containing bedaquilinie and pretomanid in a mouse model of tuberculosis. Antimicrobial Agents and Chemotherapy. 2016;60(1):17.","DOI":"10.1128\/AAC.01691-15"},{"key":"9413_CR8","doi-asserted-by":"publisher","unstructured":"Almeida D, Converse PJ, Li S, Upton AM, Fotouhi N, Nuermberger EL. Comparative Efficacy of the Novel Diarylquinoline TBAJ-876 and Bedaquiline against a Resistant Rv0678 Mutant in a Mouse Model of Tuberculosis. Antimicrob Agents Chemother. 2021. 65:10.1128\/aac.01412-21. https:\/\/doi.org\/10.1128\/aac.01412-21.","DOI":"10.1128\/aac.01412-21"},{"issue":"7","key":"9413_CR9","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.bmc.2019.02.026","volume":"27","author":"HS Sutherland","year":"2019","unstructured":"Sutherland HS, Tong AST, Choi PJ, Blaser A, Conole D, Franzblau SG, et al. 3,5-Dialkoxypyridine analogues of bedaquiline are potent antituberculosis agents with minimal inhibition of the hERG channel. Bioorg Med Chem. 2019;27(7):1292\u2013307.","journal-title":"Bioorg Med Chem"},{"issue":"10 Suppl 2","key":"9413_CR10","first-page":"S231","volume":"3","author":"W Fox","year":"1999","unstructured":"Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications. Int J Tuberc Lung Dis. 1999;3(10 Suppl 2):S231\u201379.","journal-title":"Int J Tuberc Lung Dis"},{"issue":"17","key":"9413_CR11","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1056\/NEJMoa1407426","volume":"371","author":"SH Gillespie","year":"2014","unstructured":"Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014;371(17):1577\u201387.","journal-title":"N Engl J Med"},{"issue":"18","key":"9413_CR12","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1056\/NEJMoa2033400","volume":"384","author":"SE Dorman","year":"2021","unstructured":"Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, et al. Four-month rifapentine regimens with or without moxifloxacin for tuberculosis. N Engl J Med. 2021;384(18):1705\u201318.","journal-title":"N Engl J Med"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-025-09413-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09413-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09413-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:15:07Z","timestamp":1770124507000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13063-025-09413-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9413"],"URL":"https:\/\/doi.org\/10.1186\/s13063-025-09413-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7298866\/v1","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]},"assertion":[{"value":"5 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All relevant country ethics committee\/Institutional Review Board (REC\/IRB) approvals were obtained before commencement of this study. The study protocol, the participant information and consent form (ICF), the DDC, up-to-date versions of the Investigator Brochures or Summary of Product Characteristics (SmPC), and principal investigators\u2019 qualifications have been submitted and approved by the ethical boards and regulatory authorities listed in Table\u00a0\n                      \n                      . Informed consent materials are included in supplementary materials.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"102"}}