Platform Assessing Regimens and Durations In a Global Multisite Consortium for TB

Inclusion Criteria: 1. Age 18 years or above at screening (or above age of legal consent at screening, if this is higher than 18 years in the jurisdiction in which the study is taking place) 2. Clinical evidence of active TB disease, meeting either or both of the following criteria: * Symptoms consistent with pulmonary TB at screening AND/OR * Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 7 days prior to screening 3. At least one sputum specimen produced at screening tested on Xpert MTB/RIF Ultra that has: * a semi-quantitative result of 'medium' or 'high' AND * does not show rifampicin resistance 4. Body weight within the range of 30 to 100kg and body mass index within the range of 15 to 40kg/m2 5. Willing to comply with study visits, all study procedures and treatment observation 6. Resident at a fixed address that is readily accessible for visiting, within feasible travelling distance to the site and likely to remain resident there for the duration of trial follow-up 7. Has provided written informed consent Exclusion Criteria: 1. Taken more than 1 daily dose of medication with anti-tuberculous activity during the 14 days prior to randomisation (isoniazid, rifampicin, pyrazinamide, ethambutol; linezolid, moxifloxacin, levofloxacin or amikacin) (for Phase 2b and Phase 2c) 2. Known isoniazid resistance (at sites where national isoniazid monoresistance is greater than 10% rapid testing at screening is mandated; at other sites rapid testing at screening is optional) 3. Known or suspected extra-thoracic TB, miliary TB or disseminated TB (in the judgement of the investigator; note uncomplicated pleural effusion occupying \<50% of hemithorax or concomitant intra- or extra-thoracic lymphadenopathy are not exclusions) 4. Severe clinical pulmonary TB e.g. respiratory failure or complications likely to require hospital admission in the opinion of the investigator 5. Poor general condition (Karnofsky score ≤50) OR where any delay in treatment cannot be tolerated in the opinion of the investigator 6. Active malignancy requiring systemic therapy, radiotherapy or palliative therapy 7. History of myocardial infarction, coronary heart disease or congestive cardiac failure; long QT syndrome or clinically significant arrhythmias; pulmonary hypertension; any known congenital cardiac problems; family history of long QT syndrome or sudden death from unknown or cardiac related cause; uncontrolled arterial hypertension (not excluded if this is corrected prior to randomisation) 8. Vitiligo 9. History of seizure(s) 10. Current tendinitis (any cause) or history of tendinopathy associated with fluoroquinolone use 11. History of vascular aneurysm 12. Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities 13. Current alcohol or illicit drug use sufficient to compromise the safety of the participant or research staff or compromise adherence to study procedures, in the opinion of the investigator 14. Any current or recent use of amphetamines or methamphetamines, either reported or evident on toxicity screen, if performed 15. Any other medically or socially significant condition (e.g. psychiatric illness, chronic diarrhoeal disease, metabolic condition, other cardiovascular disease not listed under criterion 7), that would, in the opinion of the investigator, compromise the participant's safety or outcome in the trial; or lead to poor compliance with study visits and protocol requirements; or compromise the interpretation of trial safety and efficacy endpoints 16. Women who are currently pregnant or breast-feeding 17. Women of childbearing potential unwilling or unable to use appropriate effective contraception during the study intervention period and for at least 14 days after the last dose of study intervention; and unwilling to commit to refrain from donating eggs (ova, oocytes) for the purpose of reproduction during this period; definitions of childbearing potential and appropriate effective contraception given below\*\* 18. Men who are unwilling to use a condom during the study period and for at least 90 days after the last dose of study drug during any activity that allows for the passage of ejaculate to another person; and are unwilling to commit to refrain from donating fresh unwashed semen 19. Known allergy to one or more of the study drugs 20. Taking a concomitant medication that has a known or predicted interaction with any of the study drugs to which the participant might be randomised. The participant need not be excluded if: 1. the concomitant medication can be stopped or replaced with an alternative non-interacting medication, if needed AND 2. the investigator judges there to be no residual clinical risk to the participant after stopping the concomitant medication (taking into account the washout period of 5x the half-life of the concomitant medication and the duration of the effect of the interaction on levels of study medication) 21. Taking a concomitant medication that is known to prolong the QTc interval. The participant need not be excluded if the concomitant medication can be stopped or replaced with an alternative medication, if needed, and the duration of the QTc prolongation is expected to resolve prior to dosing of study medication (taking into account the washout period of 5x the half-life of the concomitant medication) 22. Treatment with any immunosuppressive drugs within the 2 weeks prior to screening (taking systemic corticosteroids for less than 5 consecutive days and stopped at or prior to screening are not an exclusion; topical or inhaled steroids that are taken at a dose below the threshold considered to have systemic immunosuppressive effects are not excluded) 23. Participation in other clinical intervention trial with an investigational agent within 8 weeks prior to the first dosing day in this trial 24. 12-lead ECGs at screening or at baseline shows QTcF \>450ms (men) or \>460ms (women) calculated by Fridericia's formula; and/or any other clinically significant abnormality such as arrhythmia or ischaemia 25. Any of the following laboratory parameters at screening: 1. Haemoglobin \< 9g/dl 2. Platelet count \< 50 x 109 cells/L 3. Absolute neutrophil count \<1000 cells/μL 4. Creatinine clearance of \<75ml/min, calculated using Cockcroft-Gault equation\* 5. ALT or AST \> 3 times the upper limit of normal 6. Total bilirubin \> 1.5 times upper limit of normal 7. Serum potassium \<3.5 mmol/L (not excluded if corrected to above this level) 8. Serum magnesium \< 0.70mmol/L (not excluded if corrected to above this level) 9. Serum calcium (corrected for albumin level) \< 2.10 mmol/L (not excluded if corrected to above this level) 26. Hepatitis B surface antigen positive (known, or on a test performed at screening) 27. HIV antibody positive (known, or on test performed at screening)\* 28. Known Hepatitis C virus infection (unless also known to have negative PCR test)\*