PanACEA - STEP2C -01

Inclusion Criteria:

1. Provide written, informed consent prior to all trial-related procedures includingHIV testing.

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, previously untreated, drug susceptible pulmonary TB: presence ofMTB complex and rapid molecular tests result confirming susceptibility to RIF andINH such as GeneXpert and/or HAIN MTBDR plus. Participants who had a previoushistory of TB may be enrolled in this trial, if they:

• had a good treatment response in the opinion of the investigator; i.e. TBsymptoms improved sufficiently or resolved suggesting a cure of the pastepisode; AND

• no persistent microbiological positivity is seen (in case microbiologicalresults are available); AND - their treatment course was completed AND

• the last dose of treatment was more than 3 months ago.

5. A chest X-ray (no older than 2 weeks) which shows abnormalities that, in the opinionof the Investigator, are consistent with TB.

6. Sputum positive on microscopy from concentrated sputum for acid-fast bacilli (atleast 1+ on the IUATLD/WHO scale) AND/OR positive GeneXpert MTB/RIF Ultra®semi-quantitative result "medium" or "high" on at least one sputum sample.

7. The participant understands the interaction between the study drugs and certainfoods and is willing to forgo the consumption of those foods for the period of studymedication.

8. The participant is not of child-bearing potential or is willing to use effectivemethods of contraception when engaging in heterosexual intercourse, as definedbelow:

9. Non-childbearing potential: i. Female participant/sexual partner of male participant: Bilateral oophorectomy,and/or hysterectomy or bilateral tubal ligation more than 12 months ago and/or hasbeen postmenopausal with a history of no menses for at least 12 consecutive monthsand confirmed by a FSH test. ii. Male participant/sexual partner of female participant: Vasectomised or has had abilateral orchidectomy minimally three months prior to screening iii. Maleparticipants having a pregnant female partner or a male sexual partner: At least onebarrier method has to be used in this case. b. Effective contraception methods: i. Female participants: Two methods, includingmethods that the participant's sexual partner(s) use. At least one must be a barriermethod. Contraception must be practised for at least until 12 weeks after the lastdose of experimental treatment. For stage 3, female participants of child-bearingpotential must have used contraception if any sexual intercourse has occurred afterlast menses or within the last 3 weeks (whichever is later) before participation,and agree to use non-user dependent contraception: depo-provera injection* or anintrauterine device additional to one barrier method.

*Including a back-up method of contraception for at least 7 days to preventunintended pregnancy if injection has been administered within the first 5 days oftheir menstrual cycle. Otherwise, a back-up barrier method of contraception isrequired for one month to prevent unintended pregnancy. ii. Male participants: Two methods, including methods that the participant's femalesexual partner(s) use. At least one must be a barrier method. Effectivecontraception must be ensured for at least 12 weeks after the last dose ofexperimental treatment.

Exclusion Criteria:

1. Circumstances that raise doubt about free, unconstrained consent to studyparticipation (e.g., person in detention or person with mental disability)

2. Poor general condition where delay in treatment cannot be tolerated or death withinfour months is likely.

3. Circumstances (in the opinion of the investigator) that raise doubt about ability tocomplete the follow-up during the study period.

4. The participant is pregnant or breast-feeding or planning to become pregnant in thestudy period.

5. The participant is infected with HIV with a CD4 count <220 cells/mm3. If >220cells/mm3, participants will be included only if any of the following is applicable:

• The participant is antiretroviral (ARV) naïve and able to postpone commencing HIVtreatment for 2 months after the trial has started and then restrict regimens tothose mentioned in section on ARVs or

• The participant is ARV experienced (has been on ARV´s a minimum of 5 months), AND:ARV treatment is compliant to, or can be modified as described in the section onAntiretroviral Therapy

6. The participant has a known intolerance to any of the study drugs or concomitantdisorders or conditions for which study drugs or standard TB treatment arecontraindicated.

7. The participant has a history of, or current evidence of clinically relevantcardiovascular metabolic, gastrointestinal, neurological, hepato-biliary, renal,psychiatric or endocrine diseases, malignancy, or any other condition that willinfluence treatment response, study adherence or survival in the judgement of theinvestigator, especially: a. Neuropathy, or significant psychiatric disorder like depression or schizophrenia;especially if treatment for those has ever been required or is anticipated to berequired b. Evidence of clinically significant extra-pulmonary TB (e.g. miliary TB,TB meningitis, but not limited lymph node involvement) c. Serious lung conditionsother than TB, or significant respiratory impairment in the discretion of theinvestigator d. Uncontrolled diabetes mellitus or diabetes mellitusreceiving/requiring treatment with metformin or sulfonylureas e. Cardiovasculardisease such as myocardial infarction, heart failure, coronary heart disease,arrhythmia, tachyarrhythmia, or pulmonary hypertension f. Uncontrolled arterialhypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure of ≥95 mmHg on two occasions during screening. An attempt at antihypertensive treatmentduring the screening period is permitted). g. Long QT syndrome or family history of long QT syndrome or family history ofsudden death of unknown or cardiac-related cause h. Alcohol, regular opiate, orother drug abuse that is sufficient to significantly compromise the safety orcooperation of the participant, that includes substances prohibited by the protocolor has led to significant organ damage at the discretion of the investigator; AND/ORany abuse of methamphetamine. i. History of optic neuropathy j. Vitiligo

8. Any of the following laboratory findings at screening: a. Serum amino aspartate transferase (AST) and/or alanine aminotransferase (ALT) >3xthe upper limit of normal (ULN), b. Serum alkaline phosphatase or y-glutamyltransferase > 2.5x the ULN, c. Serum total bilirubin level >1.5x the ULN d.Estimated creatinine clearance -eCrCl (using the CKD-EPI 2021 creatinine formula):

• Stage 1: Lower than 30 ml/min)

• Stage 2: Lower than 30ml/min or lower than 60 ml/min in participants living withHIV

• Stage 3: Lower than 80ml/min e. Proteins in urine dipstick >=2+ f. Haemoglobinlevel <7.0 g/dl g. Platelet count <50,000/mm3, h. Serum potassium below 3 mmol/l,persisting after correction.

9. ECG findings in the screening ECG: (one or more):

10. QTcF of >450 milliseconds

11. Atrioventricular (AV) block with PR interval > 200 milliseconds

12. QRS complex > 120 milliseconds

13. Any other changes in the ECG that are clinically relevant as per discretion ofthe investigator

14. Restricted medication:

15. Treatment with any other investigational drug within 2 month prior to enrolmentor enrolment into other clinical (intervention) trials during participation.

16. Previous anti-TB treatment with drugs active against MTB within the last 3months prior to screening.

17. Unable or unwilling to abide by the requirements regarding restrictedmedication or have taken restricted medication. Restricted medication includesthe following drug classes, with relevant timing of intake, and possibleexceptions. Exceptions may be permissible after discussion with the sponsormedical expert.