This open label, phase 2B/C , randomized, controlled platform trial, will evaluate experimental arms including an increased dose of rifampicin, an optimized dose of pyrazinamide, moxifloxacin and sutezolid, in adult subjects with newly diagnosed, smear-positive pulmonary tuberculosis A total of up to 360 adult (≥ 18 years of age) participants will be enrolled. In case of a high number of dropouts or non-evaluable participants, it may be necessary to recruit more participants into the study. Also, if the stage 2 starts later than stage 1, it will be necessary to increase the number of control arm participants to achieve a 1:1 ratio of concomitantly recruited control and arm 4 participants (see sample size considerations).~In stage 1, participants will be randomly allocated to the control or one of the 2 rifampicin-containing experimental regimens in the ratio 1:1:1.~Arm 1: rifampicin 2,100mg, isoniazid 300mg, pyrazinamide 1,600mg moxifloxacin 600mg; given once daily for 17 weeks (3R2100HZM600)~Arm 2: rifampicin 2,100mg, isoniazid 300mg, pyrazinamide 2,000mg/2,400mg, moxifloxacin 600mg; given once daily for 12 weeks (3R2100HZoptM600).~Arm 3: control arm (2HRZE-4RH).~In stage 2, the experimental arm 4 containing sutezolid will be added. Participants will be allocated to control or one of the three experimental regimens in the ratio 1:1:1:1.~Arm 3: control-arm from (2HRZE-4RH), same as in stage 1~Arm 4: sutezolid 1200mg, delamanid 200 mg, bedaquiline 200/100mg, moxifloxacin 400mg; given once daily for 17 weeks (SDBM).
This is a phase 2B/C, open label platform study that will compare the efficacy, safety of 3 experimental regimens with a standard control regimen in participants with newly diagnosed, drug sensitive pulmonary tuberculosis. In stage 1, participants will be randomly allocated to the control or one of the 2 rifampicin-containing experimental regimens in the ratio 1:1:1. In stage 2, the experimental arm 4 containing sutezolid will be added. Participants will be allocated to control or one of the three experimental regimens in the ratio 1:1:1:1. Towards the end of stage 2, when experimental arms 1 and 2 will be fully enrolled, participants will be randomized 1:1 to control and experimental arm 4. The objective is to evaluate the efficacy, safety, and tolerability of increased dose of rifampicin, an optimized dose of pyrazinamide, moxifloxacin, and sutezolid, in adult subjects with newly diagnosed, smear-positive pulmonary tuberculosis.