A Pan-TB Regimen Targeting Host and Microbe

Inclusion Criteria:

1. Aged 18 to 65 years

2. Willing and able to provide signed written consent prior to undertaking anytrial-related procedures, or, in the case of illiteracy, witnessed oral consent

3. Body weight (in light clothing without shoes) between 30 and 90 kg.

4. Radiographic evidence of pulmonary tuberculosis

5. Positive Xpert TB/RIF (original or Ultra) for MTB

6. RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation

7. If sexually active, willing to use an effective contraceptive method for theduration of tuberculosis treatment

8. HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count ≥100/µl and eitherreceiving ART or willing to start ART during study participation

9. SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinatedagainst Covid-19 or with D-dimer <0.8 ug/ml

10. Willing to adhere to a diet excluding tyramine-rich foods (certain mold-ripenedcheeses and cured meats), and to avoid eating grapefruits and pomelos

Exclusion Criteria:

1. Any condition for which participation in the trial, as judged by the investigator,could compromise the well-being of the subject or prevent, limit or confoundprotocol specified assessments

2. Current or imminent (within 24 hr) treatment for malaria.

3. Pregnant or nursing

4. Is critically ill, and in the judgment of the investigator has a diagnosis likely toresult in death during the trial or the follow-up period.

5. TB meningitis or spondylitis, or other forms of severe tuberculosis with high riskof a poor outcome as judged by the investigator.

6. History of allergy or hypersensitivity to any of the trial therapies or relatedsubstances.

7. Having participated in other clinical trials with investigational agents within 8weeks prior to trial start or currently enrolled in an investigational trial.

8. Prior TB treatment in the preceding 6 months

9. Angina pectoris requiring treatment with nitroglycerin or other nitrates

10. Cardiac arrhythmia requiring medication, or any clinically significant ECGabnormality, in the opinion of the investigator

11. History of unstable Diabetes Mellitus requiring hospitalization for hyper- orhypo-glycaemia within the past year prior to start of screening.

12. Use of systemic corticosteroids within the past 28 days.

13. Patients requiring treatment with medications not compatible with rifampin, such asHIV-1 protease inhibitors

14. Patients requiring treatment with antidepressants, including MAO inhibitors andSSRIs.

15. Subjects with any of the following abnormal laboratory values:

16. HBsAg positive

17. creatinine >2 mg/dL

18. hemoglobin <8 g/dL

19. platelets <100x109 cells/L

20. serum potassium <3.5 mM/L

21. alanine aminotransferase (ALT) ≥2.0 x ULN

22. alkaline phosphatase (AP) >5.0 x ULN

23. total bilirubin >1.5 mg/dL

24. random blood glucose >200 mg/dL