A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis

Inclusion Criteria: 1. Able to provide written informed consent prior to initiation of any trial-related procedures or treatments, and able, in the opinion of the investigator, to comply with all trial requirements (if under 18 years of age: participant assent AND parent/legal guardian consent are required). 2. Male or female participants aged ≥14 years at screening. 3. Body weight ≥30.0 kg at screening. 4. Documented pulmonary TB: Mycobacterium tuberculosis (Mtb) confirmed by Xpert MTB/RIF Ultra with a semi-quantitative result of "low," "medium," or "high" on the screening sputum sample. 5. Rifampicin resistance detected by Xpert MTB/RIF Ultra test conducted on the screening sputum. 6. Chest radiograph consistent with evidence of active TB disease, in the opinion of the investigator. 7. Able to provide a sputum sample. 8. Participants of reproductive potential (PORP) must agree to use 2 different approved methods of birth control and continue for 12 weeks after the last dose of quabodepistat (QBS) or the other drugs administered in the trial interventions. 9. Willing to have an HIV test unless a prior HIV-positive result can be confirmed. 10. Participants living with HIV must be receiving a stable antiretroviral regimen containing dolutegravir, lamivudine or emtricitabine, and tenofovir for at least 3 months before signing informed consent or assent; must have HIV-1 RNA below 200 copies/mL at screening; and must have a CD4 count greater than 100 cells/µL at screening. Exclusion Criteria: 1. Known or suspected resistance to any drugs administered in the treatment interventions (bedaquiline \[BDQ\], pretomanid \[PMD\], linezolid \[LZD\], or quabodepistat \[QBS\]) or the respective drug classes, confirmed by laboratory testing or based on epidemiologic history (e.g., known source case with resistance). 2. Prior treatment for drug-resistant TB, except where the study Medical Monitor confirms an adequate washout period for prior medications. 3. Clinical evidence of extrapulmonary TB considered severe by the investigator (e.g., pleural, pericardial, miliary, abdominal, urogenital, osteoarticular TB, or TB meningitis). 4. Laboratory test results of: ALT or AST \>2.5 × ULN; Total bilirubin \>1.5 × ULN; eGFR \<60 mL/min/1.73 m²; Hemoglobin \<8 g/dL; Platelets \<100,000 cells/µL; White blood cell count \<2.0 × 10⁹/L; Absolute neutrophil count \<1,000 cells/µL; and HbA1c \>9.0%. 5. Pre-existing peripheral neuropathy (Grade ≥1), optic neuritis, or any visual impairment that could prevent reliable monitoring or safety assessments (including but not limited to loss of red-green color discrimination, dense cataracts, optic disc changes, or newly developed central scotomas). 6. Co-enrollment in other therapeutic clinical trials. Use of an investigational drug within 90 days preceding trial entry will be assessed case-by-case. 7. QTcF \>450 msec (males) or \>470 msec (females); atrioventricular block II or III; bifascicular block at screening; current or history of clinically significant ventricular arrhythmias; family history of long QT syndrome or sudden death; or other ECG abnormalities considered clinically significant by the investigator. 8. History of, or current, clinically relevant cardiovascular disorder, including heart failure, coronary heart disease, uncontrolled hypertension, arrhythmia, history of aortic aneurysm, or symptoms strongly suggestive of such a problem (e.g., syncope or palpitations), tachyarrhythmia, or status post myocardial infarction. 9. Known bleeding disorders or family history of bleeding disorders. 10. Any underlying condition that could interfere with assessment of X-ray images, sputum collection, or interpretation of sputum findings, or otherwise compromise participation (e.g., pulmonary silicosis, lung fibrosis, or other lung condition considered severe by the investigator, other than TB). 11. Known contraindication, allergy/sensitivity, intolerance, or hypersensitivity to components of trial drugs or their formulations. 12. Participants of childbearing potential who are breastfeeding or plan to breastfeed during the trial, have a positive pregnancy test before receiving the first dose of trial intervention, or plan to become pregnant during the trial. 13. Positive cocaine or other drugs-of-abuse screen (excluding prescribed stimulants/other prescribed medications and marijuana) at screening may be exclusionary. Detectable alcohol, marijuana, barbiturates, or opiates are not exclusionary if, in the investigator's documented opinion, the participant does not meet DSM-5 TR criteria for moderate-to-severe substance use disorder, does not pose safety/interpretability concerns, and participation is agreed to by the Medical Monitor prior to treatment. 14. History of serious mental disorders that, in the opinion of the investigator, would exclude participation. 15. Karnofsky score \<60 at screening. 16. Body mass index (BMI) \<16.0 kg/m². 17. Evidence of clinically significant metabolic, renal, gastrointestinal, neurological, psychiatric, endocrine (e.g., uncontrolled diabetes), or liver disease (e.g., clinically significant hepatitis B or C disease); malignancy; or other abnormalities that would preclude ability to participate and complete the trial, including a history of tendon disorders or prior tendinopathy/tendon rupture. 18. Evidence of pulmonary silicosis, lung fibrosis, or other lung/respiratory condition considered severe by the investigator (other than TB). 19. Receiving prohibited medications (see protocol Section 6.6.1) within specified periods or likely to require prohibited concomitant therapy during the trial. 20. Significant medical comorbidities that, in the opinion of the investigator, should preclude trial participation. 21. Donation of blood or plasma within 30 days prior to dosing. 22. Current use of herbal remedies or traditional medicines.