Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis

A phase 2, two-part, multicentre, open label, controlled, randomised clinical trial in adult participants with newly diagnosed, sputum-positive pulmonary drug-sensitive tuberculosis (DSTB). Assessing the Safety and Efficacy of TBAJ-587 as Part of a Combination Regimen in Newly Diagnosed, Drug-Sensitive, Sputum-Positive Pulmonary Tuberculosis

Inclusion Criteria: * To be eligible to participate in this trial, an individual must meet all the following criteria: 1. Provide written informed consent. 2. Male or female aged 18-65 (inclusive) 3. Clinical evidence of active TB disease, meeting either or both of the following criteria: 1. Symptoms consistent with pulmonary TB at screening AND/OR 2. Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 15 days prior to screening. 4. At least one sputum specimen produced at screening tested on either of the following: Xpert MTB/XDR and Ultra with: * positive for M. tb * a semi-quantitative result of 'medium' (cycle threshold value of \>16-22) or 'high' (cycle threshold value of \>16-22) AND * does not show rifampicin and/or isoniazid resistance. OR a. Sputum smear * Sputum positive for tubercle bacilli (at least 1+ on the IUATLD/WHO scale on smear microscopy) AND o Sensitive to rifampicin and isoniazid by rapid sputum-based test. 5. Able to produce a spot sputum with a volume of at least 4 ml. 6. Body weight within the range of 30 to 100 kgs and body mass index within the range of 15 to 40 kg/m2. 7. Newly diagnosed and untreated for this episode of TB. 8. Individuals with a history of TB may be enrolled in this trial if they meet the following criteria: 1. had a good treatment response in the opinion of the investigator (previous TB symptoms improved sufficiently or resolved) AND 2. completed their previous TB treatment AND 3. received their last dose of treatment more than 6 months before trial treatment AND • remained clinically well after completing treatment for their previous TB. 9. Willing to abstain from alcohol and tyramine containing foods for the treatment duration. 10. Willing to comply with study visits, all study procedures and treatment observation. Exclusion Criteria: * An individual who meets any of the following criteria will be excluded from participation in this trial: 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). 2. Known or suspected extra-thoracic TB, miliary TB or disseminated TB (in the judgement of the investigator; note uncomplicated pleural effusion occupying \450 ms (men) or \>460 ms (women) calculated by Fridericia's formula; and/or any other clinically significant abnormality such as arrhythmia or ischaemia. 27. Any of the following laboratory parameters at screening: 1. Hemoglobin \< 9 g/dl 2. Platelet count \< 100 x 109 cells/L 3. Absolute neutrophil count \ 1.5 times the ULN 7. Serum potassium \8.0% 28. Hepatitis B surface antigen positive (known, or on a test performed at screening), hepatitis A IgM and hepatitis C antibodies. (Participants with positive hepatitis C antibodies but negative PCR can be allowed in the trial) 29. Human Immunodeficiency Virus (HIV) antibody positive (known, or on test performed at screening) unless ALL of the following conditions are met: 1. Viral load (HIV-RNA) below 200 copies/mL on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days). 2. CD4 count \> 200 cells/mm3 on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days). 3. The participant has been taking a regimen of dolutegravir (DTG), tenofovir (TFV) and lamivudine(3TC)/emtricitabine for at least 6 months prior to screening with good adherence. 30. For Part B only: Participants unwilling or unable to disclose information regarding their last unprotected sexual intercourse (UPSI), or whose responses are considered unreliable or non-compliant by the Investigator.