xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05971602</url>
    </required_header>
    <id_info>
      <org_study_id>Gates MRI-TBD06-201</org_study_id>
      <nct_id>NCT05971602</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety Evaluation of Two to Four Months of Treatment With the Combination Regimens of DBOS and PBOS in Adults With Pulmonary Tuberculosis</brief_title>
    <official_title>A Phase 2b/c, Multi-Arm, 2-Stage, Duration Randomized Trial of the Efficacy and Safety of Two to Four Months Treatment With Regimens Containing Bedaquiline, OPC-167832, and Sutezolid, Plus Either Pretomanid or Delamanid, in Adults With Pulmonary Tuberculosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Bill &amp; Melinda Gates Medical Research Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Global Alliance for TB Drug Development</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Janssen Pharmaceutica</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Otsuka Pharmaceutical Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Bill &amp; Melinda Gates Medical Research Institute</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This multicenter, two-stage, open-label, randomized trial will aim to assess the efficacy,&#xD;
        safety, optimal duration, and pharmacokinetics (PK) of Delamanid, Bedaquiline, OPC-167832,&#xD;
        and Sutezolid (DBOS) and Pretomanid, Bedaquiline, OPC-167832, and Sutezolid (PBOS) in adult&#xD;
        participants with drug sensitive tuberculosis (DS-TB) and rifampicin or multi-drug resistant&#xD;
        TB (RR/MDR-TB).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 26, 2023</start_date>
    <completion_date type="Anticipated">March 2027</completion_date>
    <primary_completion_date type="Anticipated">March 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Stage 1: Percentage of participants with DS-TB reporting severe Adverse events (AEs) (≥ Grade 3) and/or Serious adverse events (SAEs), by treatment group</measure>
      <time_frame>Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Stage 1: Percentage of participants with pulmonary DS-TB with unfavorable outcome, by treatment group</measure>
      <time_frame>At Week 17 for DBOS and PBOS; at Week 26 for 2HRZE/4HR</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration ; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stage 2: Percentage of participants with DS-TB reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Up to Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group</measure>
      <time_frame>At 12 months post-randomization</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants reporting all-cause trial treatment discontinuation, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with pulmonary DS-TB and Human immunodeficiency virus (HIV) co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting all-cause trial treatment discontinuation, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group</measure>
      <time_frame>At 12 months post-randomization</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with DS-TB and HIV co-infection reporting unfavorable outcome, by treatment group</measure>
      <time_frame>At Week 17 for DBOS and PBOS; at Week 26 for 2HRZE/4HR</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants reporting unfavorable outcome, by treatment group</measure>
      <time_frame>At 6 months post-randomization</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Time to sustained sputum culture conversion to negative for Mtb growth in Mycobacteria Growth Indicator Tube (MGIT) culture in participants receiving combination of DBOS and PBOS relative to 2HRZE/4HR</measure>
      <time_frame>Up to Week 28</time_frame>
      <description>Hazard ratio for time to sustained sputum culture conversion to negative will be assessed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Mean change from Baseline in sputum MGIT culture time to detection (TTD) in participants receiving combination of DBOS and PBOS relative to 2HRZE/4HR</measure>
      <time_frame>Baseline and at Weeks 4, 8, 9, 13, and 17</time_frame>
      <description>Mean change from Baseline in sputum MGIT culture time to detection (TTD) will be assessed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with sustained sputum culture conversion in MGIT culture through Week 26, by treatment group</measure>
      <time_frame>Through Week 26 post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Time to sustained sputum culture conversion to negative in solid culture, by treatment group</measure>
      <time_frame>Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants with sustained sputum culture conversion in solid culture, by treatment group</measure>
      <time_frame>Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Percentage of participants developing resistance against each drug</measure>
      <time_frame>Up to 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric mean concentration of DBOS in participants with pulmonary DS-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric mean concentration of PBOS in participants with pulmonary DS-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric mean concentration of DBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric mean concentration of PBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric coefficient of variation of DBOS in participants with pulmonary DS-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric coefficient of variation of PBOS in participants with pulmonary DS-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric coefficient of variation of DBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 1: Geometric coefficient of variation of PBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with DS-TB receiving XBOS reporting all-cause trial treatment discontinuation</measure>
      <time_frame>Week 9 through 17</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with DS-TB receiving 2HRZE/4HR reporting all-cause trial treatment discontinuation</measure>
      <time_frame>Up to week 26</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with DS-TB reporting Severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Up to Week 11, Week 13, Week 15, Week 17, and Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting all-cause trial treatment discontinuation, by treatment group</measure>
      <time_frame>Up to Week 9, Week 11, Week 13, Week 15, and Week 17 for XBOS treatment groups; up to Week 26 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with RR/MDR-TB reporting severe AEs (≥ Grade 3) and/or SAEs in participants who receive XBOS for four months</measure>
      <time_frame>Up to 19 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with RR/MDR-TB reporting severe AEs (≥ Grade 3) and/or SAEs in participants who receive XBOS for four months</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with RR/MDR-TB reporting all-cause trial treatment discontinuation in participants who receive XBOS for four months</measure>
      <time_frame>Up to 17 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group</measure>
      <time_frame>Week 9, Week 11, Week 13, Week 15, and Week 17 for XBOS treatment groups; at Week 26 for 2HRZE/4HR</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration ; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting unfavorable outcome, by treatment group</measure>
      <time_frame>Through 12 months post-randomization</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants reporting unfavorable outcome, by treatment group</measure>
      <time_frame>At 6 months post-treatment after randomized duration of treatment</time_frame>
      <description>Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Time to sustained sputum culture conversion to negative for Mtb growth in MGIT culture in participants receiving combination of XBOS relative to 2HRZE/4HR</measure>
      <time_frame>Up to Week 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Mean change from Baseline in sputum MGIT culture TTD in participants receiving combination of XBOS relative to 2HRZE/4HR</measure>
      <time_frame>Baseline and at Weeks 4, 8, 9, 11, 13, 15, and 17</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with sustained sputum culture conversion to negative at Week 8 and end of treatment, by treatment group</measure>
      <time_frame>At Week 8 for all treatment groups; at Week 9, Week 11, Week 13, Week 15, and Week 17 for all XBOS treatment groups; at Week 26 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Time to sustained sputum culture conversion to negative in solid culture in participants receiving combination of XBOS relative to 2HRZE/4HR</measure>
      <time_frame>Up to Week 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants with sustained sputum culture conversion in solid culture, by treatment group</measure>
      <time_frame>Up to Week 11, Week 13, Week 15, Week 17, and Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Percentage of participants developing resistance against each drug</measure>
      <time_frame>Up to 12 months post-randomization</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Geometric mean concentration of XBOS in participants with pulmonary DS-TB and RR/MDR-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Geometric mean concentration of XBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Geometric coefficient of variation of XBOS in participants with pulmonary DS-TB and RR/MDR-TB</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Stage 2: Geometric coefficient of variation of XBOS in participants with DS-TB and HIV co-infection</measure>
      <time_frame>Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12</time_frame>
    </secondary_outcome>
    <number_of_arms>10</number_of_arms>
    <enrollment type="Anticipated">514</enrollment>
    <condition>Pulmonary Tuberculosis</condition>
    <arm_group>
      <arm_group_label>Stage 1: Arm 1: DS-TB Participants receiving DBOS for 4 months (17 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 1: Arm 2: DS-TB Participants receiving PBOS for 4 months (17 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 1: Arm 3: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E) - refers to standard regimen of 8 weeks of HRZE followed by 18 weeks of HR (2HRZE/4HR)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 1: DS-TB Participants receiving XBOS for 2 months (9 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Pretomanid or Delamanid, Bedaquiline, OPC-167832, and Sutezolid (Regimen from Stage 1 that advances to Stage 2 [XBOS])</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 2: DS-TB Participants receiving XBOS for 2.5 months (11 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 3: DS-TB Participants receiving XBOS for 3 months (13 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 4: DS-TB Participants receiving XBOS for 3.5 months (15 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 5: DS-TB Participants receiving XBOS for 4 months (17 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Stage 2: Arm 6: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Observational cohort: RR/MDR-TB Participants receiving XBOS for 4 months (17 Weeks)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Delamanid, Bedaquiline, OPC-167832, and Sutezolid (DBOS)</intervention_name>
      <description>D- 300 milligram (mg) once daily (QD) for treatment duration; B- 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S- 1200 mg QD for treatment duration</description>
      <arm_group_label>Stage 1: Arm 1: DS-TB Participants receiving DBOS for 4 months (17 Weeks)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pretomanid, Bedaquiline, OPC-167832, and Sutezolid (PBOS)</intervention_name>
      <description>P- 200 mg QD for treatment duration; B- 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S- 1200 mg QD for treatment duration</description>
      <arm_group_label>Stage 1: Arm 2: DS-TB Participants receiving PBOS for 4 months (17 Weeks)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE)</intervention_name>
      <description>Fixed dose combination (FDC) of 75 mg of isoniazid, 150 mg of rifampicin, 400 mg of pyrazinamide, and 275 mg of ethambutol (HRZE) (Standard of Care [SOC]). All the doses administered will be weight-based.</description>
      <arm_group_label>Stage 1: Arm 3: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 6: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 Weeks)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pretomanid or Delamanid, Bedaquiline, OPC-167832, and Sutezolid (XBOS)</intervention_name>
      <description>X - Pretomanid 200 mg QD for treatment duration OR Delamanid 300 mg QD for treatment duration; B - 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S-1200 mg QD for treatment duration</description>
      <arm_group_label>Observational cohort: RR/MDR-TB Participants receiving XBOS for 4 months (17 Weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 1: DS-TB Participants receiving XBOS for 2 months (9 Weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 2: DS-TB Participants receiving XBOS for 2.5 months (11 Weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 3: DS-TB Participants receiving XBOS for 3 months (13 Weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 4: DS-TB Participants receiving XBOS for 3.5 months (15 Weeks)</arm_group_label>
      <arm_group_label>Stage 2: Arm 5: DS-TB Participants receiving XBOS for 4 months (17 Weeks)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          For Stage 1:&#xD;
  &#xD;
            -  Able to provide written, informed consent prior to initiation of any trial-related&#xD;
               procedures or treatments, and able, in the opinion of the Investigator, to comply with&#xD;
               all the requirements of the trial.&#xD;
  &#xD;
            -  Male or female participants between 18 and 65 years of age (inclusive) at the&#xD;
               screening visit.&#xD;
  &#xD;
            -  Body weight ≥35.0 kilograms (kg) and body mass index (BMI) ≥16.0 at the screening&#xD;
               visit.&#xD;
  &#xD;
            -  Newly diagnosed within the past 3 weeks prior to informed consent, untreated (≤4 days&#xD;
               of treatment), drug-susceptible pulmonary TB, as defined by all of the following:&#xD;
  &#xD;
                 1. Confirmation of Mtb infection: Mtb positivity on a molecular test (eg, Xpert&#xD;
                    Ultra, Hain Line probe assay [LPA]) conducted on a sputum specimen for trial&#xD;
                    screening.&#xD;
  &#xD;
                 2. Evidence of non-paucibacillary disease: ≥1+ sputum smear positivity for acid-fast&#xD;
                    bacilli using fluorescent microscopy, as defined by the International Union&#xD;
                    Against Tuberculosis and Lung Disease (IUATLD)/World Health Organization (WHO)&#xD;
                    scale, OR a Xpert Ultra semi-quantitative result of 'medium' or 'high' on the&#xD;
                    sputum specimen for trial screening.&#xD;
  &#xD;
                 3. Drug-susceptible TB: Isoniazid and rifampicin resistance not detected, as&#xD;
                    determined by a molecular test (eg, Hain LPA, Xpert Ultra, Xpert MTB/Extensively&#xD;
                    Drug Resistant [XDR]) conducted on a sputum specimen for trial screening.&#xD;
  &#xD;
                 4. Clinical signs and/or symptoms consistent with active TB in the opinion of the&#xD;
                    Investigator.&#xD;
  &#xD;
                 5. Chest radiograph consistent with active TB in the opinion of the Investigator.&#xD;
                    Note, the Investigator is permitted, but not required, to incorporate a&#xD;
                    radiologist's interpretation into their assessment of a participant's chest&#xD;
                    radiograph.&#xD;
  &#xD;
            -  Able to spontaneously produce sputum.&#xD;
  &#xD;
            -  Female participants of childbearing potential (FOCBP) must agree to use 2 approved&#xD;
               methods of contraception with their male sexual partners or abstain from heterosexual&#xD;
               intercourse throughout their participation in the trial.&#xD;
  &#xD;
            -  Male participants must agree to use an approved method of contraception with their&#xD;
               female sexual partners of childbearing potential or abstain from heterosexual&#xD;
               intercourse throughout their participation in the trial.&#xD;
  &#xD;
          For Stage 2:&#xD;
  &#xD;
          • Newly diagnosed within the past 3 weeks of informed consent, untreated (≤4 days of&#xD;
          treatment), drug-susceptible or rifampicin-/multi-drug resistant pulmonary TB, as defined&#xD;
          by all of the following:&#xD;
  &#xD;
            1. Confirmation of Mtb infection: Mtb positivity on a molecular test (eg, Xpert Ultra,&#xD;
               Hain LPA) conducted on a screening sputum specimen.&#xD;
  &#xD;
            2. Evidence of non-paucibacillary disease: ≥1+ sputum smear positivity for acid-fast&#xD;
               bacilli using fluorescent microscopy, as defined on the IUATLD/WHO scale, OR Xpert&#xD;
               Ultra semi-quantitative result of 'medium' or 'high' on the sputum specimen for trial&#xD;
               screening.&#xD;
  &#xD;
            3. Resistance pattern:&#xD;
  &#xD;
          i. For DS TB arm, isoniazid and rifampicin resistance not detected on a molecular test (eg,&#xD;
          Hain LPA, Xpert Ultra, Xpert MTB/XDR) conducted on a screening sputum specimen, OR&#xD;
  &#xD;
          ii. For RR/MDR TB arm, either rifampicin resistance (RR TB) OR rifampicin and isoniazid&#xD;
          resistance (MDR TB) detected on a molecular test (eg, Hain LPA, Xpert Ultra, Xpert MTB/XDR)&#xD;
          conducted on a screening sputum specimen.&#xD;
  &#xD;
          • Participants with RR or MDR TB must also have fluoroquinolone resistance not detected, as&#xD;
          determined by a molecular test (eg, Hain LPA second line, Xpert MTB/XDR) performed on the&#xD;
          sputum specimen for trial screening.&#xD;
  &#xD;
          d) Clinical signs and/or symptoms consistent with active TB in the opinion of the&#xD;
          Investigator.&#xD;
  &#xD;
          e) Chest radiograph consistent with active TB in the opinion of the Investigator.&#xD;
  &#xD;
          The other inclusion criteria remain the same for Stage 2.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Suspected or documented extra-thoracic TB. Confirmed or suspected lymph node TB is not&#xD;
               considered exclusionary. The presence of a pleural effusion considered not clinically&#xD;
               significant together with pulmonary TB is not exclusionary.&#xD;
  &#xD;
            -  Known, or suspected of having, resistance to a rifamycin, isoniazid, ethambutol,&#xD;
               pyrazinamide, delamanid, pretomanid, bedaquiline, linezolid, tedizolid, or sutezolid&#xD;
               either confirmed by the laboratory, or based on epidemiological history, such as a&#xD;
               known source case with said resistance.&#xD;
  &#xD;
            -  Received any prior treatment for active Mtb disease (&gt;4 days) within the past 1 year&#xD;
               of informed consent.&#xD;
  &#xD;
            -  Received any treatment with a fluoroquinolone active against Mtb (ie, levofloxacin,&#xD;
               moxifloxacin, ciprofloxacin) or an aminoglycoside for more than 14 days within the 3&#xD;
               months prior to informed consent even if the medication was given for a different&#xD;
               indication than TB treatment.&#xD;
  &#xD;
            -  Any known prior exposure to delamanid, pretomanid, bedaquiline, OPC-167832, or any&#xD;
               oxazolidinone (linezolid, tedizolid, delpazolid, or sutezolid).&#xD;
  &#xD;
            -  Evidence of an active clinically significant/uncontrolled metabolic, gastrointestinal,&#xD;
               neurological (including peripheral neuropathy), psychiatric, endocrine (including&#xD;
               uncontrolled diabetes), hematologic, ophthalmologic (particularly optic neuritis), or&#xD;
               liver disease; active malignancy; or other medical co-morbidity considered significant&#xD;
               enough by the Investigator that the participant should not enter the trial.&#xD;
  &#xD;
            -  Significant history of, or current clinically relevant cardiovascular disorder, such&#xD;
               as heart failure, coronary artery disease, uncontrolled hypertension, arrhythmia,&#xD;
               tachyarrhythmia, prolonged QT syndrome, or presence of symptom(s) strongly suggestive&#xD;
               of such a problem, such as exertional chest pressure/pain or unexplained syncope.&#xD;
  &#xD;
            -  Significant history of, or current evidence of an active clinically significant/poorly&#xD;
               controlled pulmonary disease, such as asthma, Chronic obstructive Pulmonary disease&#xD;
               (COPD), silicosis, or lung fibrosis (other than TB), considered as severe by the&#xD;
               Investigator. In particular, any underlying pulmonary condition that could&#xD;
               significantly interfere with the assessment of X-ray images, interpretation of sputum&#xD;
               findings, or otherwise compromise the participant's participation in the trial is&#xD;
               exclusionary based on the Investigator's judgement. Clinically significant&#xD;
               post-Coronavirus disease-2019 (COVID-19) pulmonary sequelae should be considered&#xD;
               exclusionary.&#xD;
  &#xD;
            -  If HIV-infected, having any of the following present:&#xD;
  &#xD;
                 1. Not on antiretroviral treatment at time of screening or taking antiretroviral&#xD;
                    treatment for &lt;3 months prior to screening, OR&#xD;
  &#xD;
                 2. Cluster of differentiation (CD)4+ T-cell count &lt;200 cells/microliter (μL) during&#xD;
                    the screening period, OR&#xD;
  &#xD;
                 3. HIV viral load &gt;200 copies/milliliter (mL) during the screening period, OR&#xD;
  &#xD;
                 4. Evidence of a currently active opportunistic malignancy or infection related to&#xD;
                    HIV other than TB that requires treatment with a prohibited concomitant&#xD;
                    medication (oral candidiasis is not exclusionary).&#xD;
  &#xD;
            -  If female, currently pregnant or breastfeeding, OR having a positive serum or urine&#xD;
               pregnancy test during the screening period, OR planning to become pregnant within the&#xD;
               12-month period after the screening period.&#xD;
  &#xD;
            -  Current significant drug and/or alcohol abuse that is likely to result in poor&#xD;
               adherence to trial requirements or that would pose a risk to the participant's&#xD;
               wellbeing during the trial.&#xD;
  &#xD;
            -  Karnofsky Performance Status scale score at screening of &lt;60.&#xD;
  &#xD;
            -  Having a disease or condition where the use of delamanid, pretomanid, bedaquiline,&#xD;
               OPC-167832, sutezolid, rifampicin, isoniazid, pyrazinamide, or ethambutol is&#xD;
               contraindicated.&#xD;
  &#xD;
            -  Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Polymerase chain&#xD;
               reaction (PCR) result on nasopharyngeal sample taken during screening. Prior history&#xD;
               of COVID-19/SARS-CoV-2 infection is not exclusionary if SARS-CoV-2 PCR performed on&#xD;
               screening sample is negative.&#xD;
  &#xD;
            -  Any of the following laboratory results during screening:&#xD;
  &#xD;
                 1. Estimated creatinine clearance &lt;60 mL/minute&#xD;
  &#xD;
                 2. Alanine transaminase (ALT) or aspartate transaminase (AST) &gt;2.5 × upper limit of&#xD;
                    normal of the clinical laboratory reference range&#xD;
  &#xD;
                 3. Total bilirubin &gt;2x upper limit of normal of the clinical laboratory reference&#xD;
                    range, at screening&#xD;
  &#xD;
                 4. Hemoglobin &lt;8.0 grams per deciliter (g/dL)&#xD;
  &#xD;
                 5. Platelet count &lt;100 x 10^9/liter (L)&#xD;
  &#xD;
                 6. White blood cell count &lt;2.0 x 10^9/L&#xD;
  &#xD;
                 7. Screening glycosylated hemoglobin (HbA1c) ≥10.0%&#xD;
  &#xD;
                 8. Positive hepatitis B surface antigen&#xD;
  &#xD;
                 9. Positive hepatitis C antibody.&#xD;
  &#xD;
            -  Moderate to severe substance use disorder according to the Diagnostic and Statistical&#xD;
               Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (substances of concern may&#xD;
               include cocaine, amphetamines, opiates, barbiturates, benzodiazepines, or alcohol).&#xD;
  &#xD;
            -  A clinically significant Electrocardiogram (ECG) abnormality at screening as confirmed&#xD;
               by a central ECG reading service. Examples of such include, but are not limited to,&#xD;
               second- or third-degree atrioventricular block, complete right bundle branch block,&#xD;
               left bundle branch block, QRS duration ≥120 millisecond (msec), QT interval corrected&#xD;
               using Fridericia's formula (QTcF) interval &gt;450 msec in males or &gt;470 msec in females,&#xD;
               atrial fibrillation or flutter, supraventricular tachycardia, and ventricular&#xD;
               tachycardia or multiple multifocal premature ventricular complexes. The following ECG&#xD;
               findings are not considered clinically significant: sinus tachycardia, mild&#xD;
               first-degree atrioventricular block (P-R interval &lt;0.23 sec), right or left axis&#xD;
               deviation, incomplete right bundle branch block, and isolated left anterior fascicular&#xD;
               block (left anterior hemiblock) in young otherwise healthy participants.&#xD;
  &#xD;
            -  Participants receiving any of the prohibited medications within the specified periods&#xD;
               or who would be likely to require prohibited concomitant therapy during the trial.&#xD;
  &#xD;
            -  History of having taken another investigational drug within 30 days preceding trial&#xD;
               entry or participates in another clinical study during the duration of this trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Gates MRI</last_name>
      <role>Study Director</role>
      <affiliation>Bill &amp; Melinda Gates Medical Research Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Gates MRI</last_name>
      <phone>+1 857 702 2108</phone>
      <email>clinical.trials@gatesmri.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Gates MRI (Toll Free Number)</last_name>
      <phone>+1 866 789 5767</phone>
    </overall_contact_backup>
    <location>
      <facility>
        <name>De La Salle Health Sciences Institute</name>
        <address>
          <city>Dasmarinas</city>
          <country>Philippines</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Tropical Disease Foundation</name>
        <address>
          <city>Makati</city>
          <country>Philippines</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Lung Center of Phillipines</name>
        <address>
          <city>Quezon City</city>
          <country>Philippines</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Bio-Medical Research Institute; Faculty of Medicine and Health Sciences, Stellenbosch University; Tygerberg Medical Campus</name>
        <address>
          <city>Cape Town</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>TASK - Central (Brooklyn)</name>
        <address>
          <city>Cape Town</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>UCT (Cape Town); General Medicine &amp; Global Health (GMGH); Hatter Heart Research Institute</name>
        <address>
          <city>Cape Town</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>UCT South African Tuberculosis Vaccine Initiative (SATVI)</name>
        <address>
          <city>Cape Town</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>University of Cape Town (UCT) Lung Institute</name>
        <address>
          <city>Cape Town</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>The Aurum Institute (Tembisa CRS)</name>
        <address>
          <city>Johannesburg</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location>
      <facility>
        <name>Perinatal HIV Research Unit (PHRU)</name>
        <address>
          <city>Klerksdorp</city>
          <country>South Africa</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location_countries>
      <country>Philippines</country>
      <country>South Africa</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Delamanid, Bedaquiline, OPC-167832, and Sutezolid (DBOS)</keyword>
    <keyword>Pretomanid, Bedaquiline, OPC-167832, and Sutezolid (PBOS)</keyword>
    <keyword>Drug sensitive tuberculosis</keyword>
    <keyword>Rifampicin-resistant tuberculosis (RR-TB)</keyword>
    <keyword>Multi-drug resistant tuberculosis (MDR-TB)</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tuberculosis</mesh_term>
      <mesh_term>Tuberculosis, Pulmonary</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rifampin</mesh_term>
      <mesh_term>Isoniazid</mesh_term>
      <mesh_term>Pyrazinamide</mesh_term>
      <mesh_term>Ethambutol</mesh_term>
      <mesh_term>Bedaquiline</mesh_term>
      <mesh_term>Diarylquinolines</mesh_term>
      <mesh_term>Oxazolidinones</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05971602
  org study id: Gates MRI-TBD06-201
  nct id: NCT05971602
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This multicenter, two-stage, open-label, randomized trial will aim to assess the efficacy,
        safety, optimal duration, and pharmacokinetics (PK) of Delamanid, Bedaquiline, OPC-167832,
        and Sutezolid (DBOS) and Pretomanid, Bedaquiline, OPC-167832, and Sutezolid (PBOS) in adult
        participants with drug sensitive tuberculosis (DS-TB) and rifampicin or multi-drug resistant
        TB (RR/MDR-TB).
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Stage 1: Percentage of participants with DS-TB reporting severe Adverse events (AEs) (≥ Grade 3) and/or Serious adverse events (SAEs), by treatment group
  time frame: Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR
  measure: Stage 1: Percentage of participants with pulmonary DS-TB with unfavorable outcome, by treatment group
  time frame: At Week 17 for DBOS and PBOS; at Week 26 for 2HRZE/4HR
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration ; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 2: Percentage of participants with DS-TB reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Up to Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR
  measure: Stage 2: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group
  time frame: At 12 months post-randomization
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 1: Percentage of participants reporting all-cause trial treatment discontinuation, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 1: Percentage of participants reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 1: Percentage of participants with pulmonary DS-TB and Human immunodeficiency virus (HIV) co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR
  measure: Stage 1: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 1: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting all-cause trial treatment discontinuation, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 1: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group
  time frame: At 12 months post-randomization
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 1: Percentage of participants with DS-TB and HIV co-infection reporting unfavorable outcome, by treatment group
  time frame: At Week 17 for DBOS and PBOS; at Week 26 for 2HRZE/4HR
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 1: Percentage of participants reporting unfavorable outcome, by treatment group
  time frame: At 6 months post-randomization
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 1: Time to sustained sputum culture conversion to negative for Mtb growth in Mycobacteria Growth Indicator Tube (MGIT) culture in participants receiving combination of DBOS and PBOS relative to 2HRZE/4HR
  time frame: Up to Week 28
  description: Hazard ratio for time to sustained sputum culture conversion to negative will be assessed
  measure: Stage 1: Mean change from Baseline in sputum MGIT culture time to detection (TTD) in participants receiving combination of DBOS and PBOS relative to 2HRZE/4HR
  time frame: Baseline and at Weeks 4, 8, 9, 13, and 17
  description: Mean change from Baseline in sputum MGIT culture time to detection (TTD) will be assessed
  measure: Stage 1: Percentage of participants with sustained sputum culture conversion in MGIT culture through Week 26, by treatment group
  time frame: Through Week 26 post-randomization
  measure: Stage 1: Time to sustained sputum culture conversion to negative in solid culture, by treatment group
  time frame: Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR
  measure: Stage 1: Percentage of participants with sustained sputum culture conversion in solid culture, by treatment group
  time frame: Up to Week 19 for DBOS and PBOS; up to Week 28 for 2HRZE/4HR
  measure: Stage 1: Percentage of participants developing resistance against each drug
  time frame: Up to 12 months post-randomization
  measure: Stage 1: Geometric mean concentration of DBOS in participants with pulmonary DS-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric mean concentration of PBOS in participants with pulmonary DS-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric mean concentration of DBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric mean concentration of PBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric coefficient of variation of DBOS in participants with pulmonary DS-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric coefficient of variation of PBOS in participants with pulmonary DS-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric coefficient of variation of DBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 1: Geometric coefficient of variation of PBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 2: Percentage of participants with DS-TB receiving XBOS reporting all-cause trial treatment discontinuation
  time frame: Week 9 through 17
  measure: Stage 2: Percentage of participants with DS-TB receiving 2HRZE/4HR reporting all-cause trial treatment discontinuation
  time frame: Up to week 26
  measure: Stage 2: Percentage of participants with DS-TB reporting Severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Up to Week 11, Week 13, Week 15, Week 17, and Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR
  measure: Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting severe AEs (≥ Grade 3) and/or SAEs, by treatment group
  time frame: Through 12 months post-randomization
  measure: Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting all-cause trial treatment discontinuation, by treatment group
  time frame: Up to Week 9, Week 11, Week 13, Week 15, and Week 17 for XBOS treatment groups; up to Week 26 for 2HRZE/4HR
  measure: Stage 2: Percentage of participants with RR/MDR-TB reporting severe AEs (≥ Grade 3) and/or SAEs in participants who receive XBOS for four months
  time frame: Up to 19 weeks
  measure: Stage 2: Percentage of participants with RR/MDR-TB reporting severe AEs (≥ Grade 3) and/or SAEs in participants who receive XBOS for four months
  time frame: Through 12 months post-randomization
  measure: Stage 2: Percentage of participants with RR/MDR-TB reporting all-cause trial treatment discontinuation in participants who receive XBOS for four months
  time frame: Up to 17 weeks
  measure: Stage 2: Percentage of participants with pulmonary DS-TB reporting unfavorable outcome, by treatment group
  time frame: Week 9, Week 11, Week 13, Week 15, and Week 17 for XBOS treatment groups; at Week 26 for 2HRZE/4HR
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration ; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 2: Percentage of participants with pulmonary DS-TB and HIV co-infection reporting unfavorable outcome, by treatment group
  time frame: Through 12 months post-randomization
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 2: Percentage of participants reporting unfavorable outcome, by treatment group
  time frame: At 6 months post-treatment after randomized duration of treatment
  description: Participants that experience one or more of the following events following randomization will be categorized as having an unfavorable outcome status: Absence of microbiological cure (positive sputum culture); Death from any cause; Permanent discontinuation of trial treatment before the end of the assigned treatment duration; Extension of TB treatment by the Investigator more than 5 days beyond the end of the assigned treatment duration for any reason; Re-start of TB treatment by the Investigator during the post-treatment follow-up period excluding documented TB re-infection with a different Mtb strain than Baseline; Positive culture for Mtb at last visit excluding documented TB re-infection with a different Mtb strain than Baseline.
  measure: Stage 2: Time to sustained sputum culture conversion to negative for Mtb growth in MGIT culture in participants receiving combination of XBOS relative to 2HRZE/4HR
  time frame: Up to Week 28
  measure: Stage 2: Mean change from Baseline in sputum MGIT culture TTD in participants receiving combination of XBOS relative to 2HRZE/4HR
  time frame: Baseline and at Weeks 4, 8, 9, 11, 13, 15, and 17
  measure: Stage 2: Percentage of participants with sustained sputum culture conversion to negative at Week 8 and end of treatment, by treatment group
  time frame: At Week 8 for all treatment groups; at Week 9, Week 11, Week 13, Week 15, and Week 17 for all XBOS treatment groups; at Week 26 for 2HRZE/4HR
  measure: Stage 2: Time to sustained sputum culture conversion to negative in solid culture in participants receiving combination of XBOS relative to 2HRZE/4HR
  time frame: Up to Week 28
  measure: Stage 2: Percentage of participants with sustained sputum culture conversion in solid culture, by treatment group
  time frame: Up to Week 11, Week 13, Week 15, Week 17, and Week 19 for XBOS treatment groups; up to Week 28 for 2HRZE/4HR
  measure: Stage 2: Percentage of participants developing resistance against each drug
  time frame: Up to 12 months post-randomization
  measure: Stage 2: Geometric mean concentration of XBOS in participants with pulmonary DS-TB and RR/MDR-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 2: Geometric mean concentration of XBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 2: Geometric coefficient of variation of XBOS in participants with pulmonary DS-TB and RR/MDR-TB
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  measure: Stage 2: Geometric coefficient of variation of XBOS in participants with DS-TB and HIV co-infection
  time frame: Pre-dose, post-dose at Weeks 1, 2, 4, 6, 9, 11, 13, 15, 17, 19, 21, 23, 26 and at Months 9, 12
  arm group label: Stage 1: Arm 1: DS-TB Participants receiving DBOS for 4 months (17 Weeks)
  arm group type: Experimental
  arm group label: Stage 1: Arm 2: DS-TB Participants receiving PBOS for 4 months (17 Weeks)
  arm group type: Experimental
  arm group label: Stage 1: Arm 3: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 weeks)
  arm group type: Experimental
  description: Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E) - refers to standard regimen of 8 weeks of HRZE followed by 18 weeks of HR (2HRZE/4HR)
  arm group label: Stage 2: Arm 1: DS-TB Participants receiving XBOS for 2 months (9 Weeks)
  arm group type: Experimental
  description: Pretomanid or Delamanid, Bedaquiline, OPC-167832, and Sutezolid (Regimen from Stage 1 that advances to Stage 2 [XBOS])
  arm group label: Stage 2: Arm 2: DS-TB Participants receiving XBOS for 2.5 months (11 Weeks)
  arm group type: Experimental
  arm group label: Stage 2: Arm 3: DS-TB Participants receiving XBOS for 3 months (13 Weeks)
  arm group type: Experimental
  arm group label: Stage 2: Arm 4: DS-TB Participants receiving XBOS for 3.5 months (15 Weeks)
  arm group type: Experimental
  arm group label: Stage 2: Arm 5: DS-TB Participants receiving XBOS for 4 months (17 Weeks)
  arm group type: Experimental
  arm group label: Stage 2: Arm 6: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 Weeks)
  arm group type: Experimental
  arm group label: Observational cohort: RR/MDR-TB Participants receiving XBOS for 4 months (17 Weeks)
  arm group type: Experimental
  intervention type: Drug
  intervention name: Delamanid, Bedaquiline, OPC-167832, and Sutezolid (DBOS)
  description: D- 300 milligram (mg) once daily (QD) for treatment duration; B- 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S- 1200 mg QD for treatment duration
  arm group label: Stage 1: Arm 1: DS-TB Participants receiving DBOS for 4 months (17 Weeks)
  intervention type: Drug
  intervention name: Pretomanid, Bedaquiline, OPC-167832, and Sutezolid (PBOS)
  description: P- 200 mg QD for treatment duration; B- 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S- 1200 mg QD for treatment duration
  arm group label: Stage 1: Arm 2: DS-TB Participants receiving PBOS for 4 months (17 Weeks)
  intervention type: Drug
  intervention name: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE)
  description: Fixed dose combination (FDC) of 75 mg of isoniazid, 150 mg of rifampicin, 400 mg of pyrazinamide, and 275 mg of ethambutol (HRZE) (Standard of Care [SOC]). All the doses administered will be weight-based.
  arm group label: Stage 1: Arm 3: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 weeks)
  arm group label: Stage 2: Arm 6: DS-TB Participants receiving 2HRZE/4HR for 6 months (26 Weeks)
  intervention type: Drug
  intervention name: Pretomanid or Delamanid, Bedaquiline, OPC-167832, and Sutezolid (XBOS)
  description: X - Pretomanid 200 mg QD for treatment duration OR Delamanid 300 mg QD for treatment duration; B - 400 mg QD for 2 weeks, 200 mg thrice weekly for remaining treatment weeks; O- 30 mg QD for treatment duration and S-1200 mg QD for treatment duration
  arm group label: Observational cohort: RR/MDR-TB Participants receiving XBOS for 4 months (17 Weeks)
  arm group label: Stage 2: Arm 1: DS-TB Participants receiving XBOS for 2 months (9 Weeks)
  arm group label: Stage 2: Arm 2: DS-TB Participants receiving XBOS for 2.5 months (11 Weeks)
  arm group label: Stage 2: Arm 3: DS-TB Participants receiving XBOS for 3 months (13 Weeks)
  arm group label: Stage 2: Arm 4: DS-TB Participants receiving XBOS for 3.5 months (15 Weeks)
  arm group label: Stage 2: Arm 5: DS-TB Participants receiving XBOS for 4 months (17 Weeks)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Gates MRI
  role: Study Director
  affiliation: Bill & Melinda Gates Medical Research Institute
  last name: Gates MRI
  phone: +1 857 702 2108
  email: clinical.trials@gatesmri.org
  last name: Gates MRI (Toll Free Number)
  phone: +1 866 789 5767
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Not yet recruiting
  facility: 
  status: Recruiting
  country: Philippines
  country: South Africa
  responsible party type: Sponsor
  mesh term: Tuberculosis
  mesh term: Tuberculosis, Pulmonary
  mesh term: Rifampin
  mesh term: Isoniazid
  mesh term: Pyrazinamide
  mesh term: Ethambutol
  mesh term: Bedaquiline
  mesh term: Diarylquinolines
  mesh term: Oxazolidinones
  sharing ipd: Yes