This is a phase 2B/C, open label platform study that will compare the efficacy, safety of 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 BTZ-043 will be added. The allocation ratio will be changed to co-enrol the remaining participants in arms 1- 3 simultaneously with arm 4 in a ratio of 1:1:1:2. When arms 1-2 are fully enrolled and arm 4 is not, further participants will be randomized 1:1 to control and experimental arm 4. Not all countries will participate in stage 2.
In stage 3, participants will be allocated in parallel to control arm treatment (now designated arm 7) or the experimental arms 5 and 6, favouring arm 5, 2:1:1 over arms 6 and control. This stage will start after completion of recruitment in the stages 1 and 2. Enrolment of participants into arm 5 will proceed following review of data from the ENABLE/UNITE-03 (NCT06748937), non-clinical safety data and after endorsement by the DSMB. Thus, arm 5 recruitment might start after arms 6 and 7, which may require an increase in the control arm sample size to ensure controls are recruited concomitantly.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Provide written, informed consent prior to all trial-related procedures including HIV testing.
. Male or female, aged between 18 and 65 years, inclusive.
. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
. Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTB complex and rapid molecular tests result confirming susceptibility to RIF and INH such as GeneXpert and/or HAIN MTBDR plus. Participants who had a previous history of TB may be enrolled in this trial, if they:
. A chest X-ray (no older than 2 weeks) which shows abnormalities that, in the opinion of the Investigator, are consistent with TB.
. Sputum positive on microscopy from concentrated sputum for acid-fast bacilli (at least 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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Time to stable culture conversion to negative in liquid media
. The participant understands the interaction between the study drugs and certain foods and is willing to forgo the consumption of those foods for the period of study medication.
. The participant is not of child-bearing potential or is willing to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
Exclusion criteria
. Circumstances that raise doubt about free, unconstrained consent to study participation (e.g., person in detention or person with mental disability)
. Poor general condition where delay in treatment cannot be tolerated or death within four months is likely.
. Circumstances (in the opinion of the investigator) that raise doubt about ability to complete the follow-up during the study period.
. The participant is pregnant or breast-feeding or planning to become pregnant in the study period.
. The participant is infected with HIV with a CD4 count \<220 cells/mm3. If \>220 cells/mm3, participants will be included only if any of the following is applicable:
. The participant has a known intolerance to any of the study drugs or concomitant disorders or conditions for which study drugs or standard TB treatment are contraindicated.
. The participant has a history of, or current evidence of clinically relevant cardiovascular metabolic, gastrointestinal, neurological, hepato-biliary, renal, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially:
. Any of the following laboratory findings at screening: