Inclusion Criteria:
1. Provide written, informed consent prior to all trial-related procedures and willing to adhere to all required study procedures and restrictions for the duration of the trial.
2. Male or female, aged between 18 and 65 years, inclusive.
3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
4. Newly diagnosed and untreated for this episode of pulmonary TB.
5. Rifampicin- and isoniazid susceptible pulmonary TB as determined by molecular testing (GeneXpert XDR or Genotype MTBDRplus for INH).
6. A chest X-ray taken during the screening period or up to 2 weeks before screening which, in the opinion of the investigator, is consistent with TB.
7. GeneXpert positive with a quantitative readout of medium or high.
8. Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).
9. Be of non-childbearing potential or of childbearing potential using effective methods of birth control, as defined in section 5.2 and in Appendix 1.
Female Participants
10. For WOCBP who are not already receiving contraception per Appendix 1 requirements, agree to receive injectable or other contraceptive methods (per Appendix 1), to be given during screening, and at least 1 day prior to first dose of IMP.
Male Participants
11. Agree to ALL of the following during the study intervention period and for at least 90 days, after the last dose of study intervention:
1. Refrain from donating fresh unwashed semen
2. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.
Exclusion Criteria:
1. Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
2. Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.
3. History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.
4. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice (with the exception of Gilbert's syndrome or asymptomatic gallstones).
5. History of hypothyroidism
6. QTcF of \>450 ms at baseline
7. Clinically significant evidence of extra-thoracic TB, as judged by the investigator.
8. History of allergy to any of the trial IMP as confirmed by the clinical judgement of the investigator.
9. Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.
10. HIV positive AND:
1. CD4 \< 250cells/mm3
2. On other ART regimen not listed below or, if not on ART they are not willing to wait to start treatment until completion of study regimen
Note: ART regimens permitted is limited to the following in line with local guidelines for 1st line ART:
* NRTIs selected from: Emtricitabine, Lamivudine, Tenofovir
* PLUS Dolutegravir 50 mg daily, or 50 mg twice daily if randomized to a rifampicin containing arm.
Participants established on ART (2 NRTIs and dolutegravir) for more than 30 days at start of screening are eligible for participation.
As the drug-drug interaction potential of ART has not been fully investigated with the IMP, NNRTIs (efavirenz, nevirapine) and other protease inhibitors will not be permitted in this study.
11. Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation and for at least 90 days after the last dose of study intervention. Male participant planning to conceive a child for at least 90 days, after the last dose of study intervention in the trial.
Treatment History
12. Participation in other clinical studies with investigational agents within 8 weeks prior to screening.
13. Treatment received for this episode of TB with any drug active against M. tb (including but not limited to isoniazid, ethambutol, cycloserine, fluoroquinolones, rifamycins, aminoglycosides, nitroimidazoles, bedaquiline, oxazolidinones, para-amino salicylic acid, pyrazinamide, thioacetazone, thioamides).
14. Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.
15. Unavoidable treatment with prohibited concomitant medications (see section 5.3.2) anticipated during administration of IMP.
Laboratory Safety Testing
16. Presence of hepatitis B surface antigen (HBsAg+)
17. Positive hepatitis C antibody test result (HCV IgG+)
18. Participants with the following toxicities at screening as defined by the enhanced CTCAE toxicity table:
1. creatinine \>1.5 times upper limit of normal (ULN)
2. haemoglobin \<8.0 g/dL
3. platelets \<50x109 cells/L
4. serum potassium \<3.0 mmol/L
5. alanine aminotransferase (ALT) ≥5 x ULN
6. total bilirubin \>1.5 x ULN; Participants with Gilbert's syndrome can be included with total bilirubin \>1.5 x ULN as long as direct bilirubin is ≤1.5xULN
7. Total white cell count \<1.5 cells/L
8. Thyroid Stimulating Hormone \> ULN
9. Glucose \< 3.5 mmol/L
