{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:35:05Z","timestamp":1789608905831,"version":"build-2803163510"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015303","name":"Otsuka Pharmaceutical Development and Commercialization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015303","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","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>Background<\/jats:title>\n                    <jats:p>\n                      Delamanid and bedaquiline are two of the most recently developed antituberculosis (TB) drugs that have been extensively studied in patients with multidrug-resistant TB. There is currently a need for more potent, less-toxic drugs with novel mechanisms of action that can be used in combination with these newer agents to shorten the duration of treatment as well as prevent the development of drug resistance. Quabodepistat (QBS) is a newly discovered inhibitor of decaprenylphosphoryl-\u03b2-D-ribose-2\u2032-oxidase, an essential enzyme for\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      to synthesize key components of its cell wall. The objective of this study is to evaluate the safety, efficacy, and appropriate dosing of a 4-month regimen of QBS in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary TB in comparison with the 6-month standard treatment (i.e., rifampicin, isoniazid, ethambutol, and pyrazinamide).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 2b\/c, open-label, randomized, parallel group, dose-finding trial will enroll approximately 120 participants (including no more than 15% with human immunodeficiency virus [HIV] coinfection) aged \u2265 18 to \u2264 65 years at screening with newly diagnosed pulmonary drug-sensitive TB from ~8 sites in South Africa. Following a screening period of up to 14 days, eligible participants will be randomized in a ratio of 1:2:2:1 to one of four arms. Randomization will be stratified by HIV status and the presence of bilateral cavitation on a screening chest x-ray. After the end of the treatment period, participants will be followed until 12 months post randomization. The primary efficacy endpoint is the proportion of participants achieving sputum culture conversion in Mycobacteria Growth Indicator Tube by the end of the treatment period. The safety endpoints consist of adverse events, clinical laboratory tests, vital signs, physical examination findings, and electrocardiographic changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>QBS\u2019s potent bactericidal activity and distinct mechanism of action (compared with other TB drugs currently available for human use) may make it an ideal candidate for inclusion in a novel treatment regimen to improve efficacy and potentially prevent resistance to concomitant TB drugs. This trial will assess the effectiveness, safety, and dosing of a new, shorter, QBS-based, combination anti-TB treatment regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial status<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05221502. Registered on February 3, 2022<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-024-07912-5","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T09:02:19Z","timestamp":1705654939000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b\/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy"],"prefix":"10.1186","volume":"25","author":[{"given":"Rodney","family":"Dawson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Diacon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simbarashe","family":"Takuva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongge","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vatsala","family":"Karwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Hafkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"7912_CR1","unstructured":"World Health Organization Global Tuberculosis Report 2022. 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The trial site(s) will seek approval by an independent ethics committee according to regional requirements. Written informed consent will be obtained from all participants prior to screening.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable \u2014 no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Informed consent materials are attached as supplementary materials.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"R. D. is an investigator for the study described in this paper, and they and\/or their institutions will receive funding support from Otsuka Pharmaceutical Development & Commercialization, Inc. to conduct this study. A. H. D. is an investigator for the study described in this paper, and their institution will receive funding support from Otsuka Pharmaceutical Development & Commercialization, Inc. to conduct this study. S. T., Y. L., B. Z., V. K., and J. H. are employees of Otsuka Pharmaceutical Development & Commercialization, Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}