TBD09 combined with other TB medicines to kill bacteria in pulmonary TB

A Phase 2, Open-Label, Multi-Group, Controlled, Randomized Trial of the Safety, Bactericidal Activity, and Pharmacokinetics of TBD09 in Combination With Other Active Agents in Adults With Drug-Sensitive Pulmonary Tuberculosis

This test will see if adding TBD09 to other TB medicines helps clear the infection in adults with drug‑sensitive pulmonary tuberculosis.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Gates Medical Research Institute (other)
• Locations: 13 sites (Durban, Bluff and 12 other locations)
• Trial ID: NCT07525427 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial tests the bactericidal activity of TBD09 when given with other active TB medicines in adults with rifampicin‑sensitive pulmonary tuberculosis. Participants receive combination regimens that include bedaquiline and pretomanid, with some arms substituting or adding an oxazolidinone (linezolid or TBD09), and will provide serial sputum samples to measure bacterial killing. Eligible adults (18–65 years) must be newly diagnosed with rifampicin‑sensitive pulmonary TB, meet weight and reproductive criteria, and have no recent anti‑TB therapy; those with recent or multiple prior TB episodes or extrapulmonary disease are excluded. Safety data and early bactericidal activity outcomes will inform whether TBD09 should proceed to larger efficacy trials.

Who should consider this trial

Good fit: Adults aged 18–65 with newly diagnosed rifampicin‑sensitive pulmonary TB who can produce sputum, meet weight and contraceptive requirements, and have no recent TB treatment are ideal candidates.

Not a fit: People with rifampicin‑resistant or extrapulmonary TB, recent or multiple prior TB treatments, or significant medical comorbidities are unlikely to receive benefit from this study.

Why it matters

Potential benefit: If successful, this could lead to a more effective regimen that kills TB bacteria faster and may shorten treatment for drug‑sensitive pulmonary tuberculosis.

How similar studies have performed: Regimens combining bedaquiline, pretomanid and oxazolidinones have shown promise in drug‑resistant TB, but TBD09 itself is a novel oxazolidinone with limited clinical data.

Eligibility criteria

Inclusion Criteria:

* Age 18-65 years at consent
* Body weight 35-100 kg at screening
* Written informed consent obtained
* Newly diagnosed rifampicin-sensitive pulmonary TB

  * Molecular confirmation of M. tuberculosis on Xpert MTB/RIF Ultra
  * ≥1+ AFB smear or Xpert Ultra low, medium, or high semi-quantitative result
  * Rifampicin sensitivity on molecular test
* Chest X-ray consistent with TB (Investigator assessment)
* Able to spontaneously produce sputum
* Reproductive requirements met
* Women of childbearing potential: 2 approved contraceptive methods or abstinence
* Males: contraception or abstinence through 90 days post-dose

Exclusion Criteria:

* Prior anti-TB treatment for the current TB episode within 60 days
* Prior medication active against Mtb within 3 months
* Evidence of extra-thoracic TB, per investigator judgement
* Prior treatment completion for TB within 3 years
* 2 or more prior episodes of TB
* Clinically significant history of or current medical condition posing safety risk
* If HIV positive:

  * Not on ARVs or taking ARVs for \<3 months prior to screening OR
  * CD4+ count \<200cells/uL at screening OR
  * HIV viral load \>200 copies /mL at screening OR
  * AIDS infection or malignancies
* Meets any of the following laboratory values during screening:

  * AST, ALT, or ALP ≥2.5× ULN
  * Total bilirubin ≥1.2× ULN
  * eGFR \<60 mL/min/1.73 m²
  * Hemoglobin \<9.0 g/dL (male) or \<8.5 g/dL (female)
  * White blood cell count \<2,000/mm³
  * Absolute neutrophil count \<800/mm³
  * Platelet count ≤100,000/mm³
  * Positive hepatitis B surface antigen
  * Positive hepatitis C antibody
  * HbA1c ≥8.0%
* Current or recent systemic immunosuppressive therapy, including corticosteroids
* Significant drug or alcohol abuse affecting compliance or safety
* Pregnant or breastfeeding, positive pregnancy test, or planning pregnancy shortly after treatment

Where this trial is running

Durban, Bluff and 12 other locations

• Enhancing Care Foundation at Wentworth Hospital — Durban, Bluff, South Africa (NOT_YET_RECRUITING)
• TASK Applied Science - Eden — George, Central, South Africa (RECRUITING)
• Clinical Research and HIV Research Unit (CHRU) @ Helen Joseph Hospital — Johannesburg, Gauteng, South Africa (RECRUITING)
• The Aurum Institute Tembisa — Tembisa, Gauteng, South Africa (NOT_YET_RECRUITING)
• CHRU @ Isango Lethemba — Bethelsdorp, Gqeberha, South Africa (RECRUITING)
• Madibeng Centre for Research — Brits, North West, South Africa (NOT_YET_RECRUITING)
• Setshaba Research Center — Pretoria, Soshangue, South Africa (NOT_YET_RECRUITING)
• ONE MRI — Cape Town, Western Cape, South Africa (RECRUITING)
• TASK Applied Science - Brookylyn Chest Hospital — Cape Town, Western Cape, South Africa (RECRUITING)
• BioMedical Research Institute - Stellenbosch University @ Tygerberg Hospital — Cape Town, Western Cape, South Africa (NOT_YET_RECRUITING)
• UCT Lung Institute — Cape Town, Western Cape, South Africa (NOT_YET_RECRUITING)
• Desmond Tutu Health Foundation — Cape Town, Western Cape, South Africa (NOT_YET_RECRUITING)
• Synergy Biomedical Research Institute (SBRI) — East London, South Africa (RECRUITING)

Study contacts

• Study coordinator: Gates MRI

Conditions: Drug Susceptible Pulmonary Tuberculosis, TBD09, oxazolidinone, bedaquiline, pretomanid, linezolid, drug-susceptible pulmonary tuberculosis