Bactericidal Activity of TBD09 in Combination With Other Drugs in Pulmonary Tuberculosis

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

The purpose of this study is to evaluate if TBD09 in combination with other active agents in adults with drug sensitive pulmonary tuberculosis has potential to be safe and effective.

Study Overview

• Status: Recruiting
• Conditions: Drug Susceptible Pulmonary Tuberculosis
• Intervention / Treatment: Drug: Bedaquiline, pretomanid and TBD09; Drug: Bedaquiline, pretomanid and TBD09; Drug: Bedaquiline, pretomanid and TBD09; Drug: Bedaquiline, pretomanid and TBD09; Drug: Bedaquiline, pretomanid and linezolid

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gates MRI; Phone Number: +1 857 702 2108; Email: clinical.trials@gatesmri.org
• Study Contact Backup: Name: Gates MRI; Phone Number: +1-866-789-5757

Study Locations

• South Africa
  • East London, South Africa, 5241
    • Recruiting
    • Synergy Biomedical Research Institute (SBRI)
    • Contact: Mookho Malahleha, MD; Phone Number: 437222306; Email: drmookho@sbri.org.za
    • Contact: Nqobile Msweli; Email: nqobile@sbri.org.za
    • Principal Investigator: Mookho Malahleha, MD
  • Bluff
    • Durban, Bluff, South Africa, 4052
      • Recruiting
      • Enhancing Care Foundation at Wentworth Hospital
      • Contact: Sundrapragasen (Sandy) Pillay, MD; Phone Number: +27 31 4611629; Email: pillay@ecarefoundation.com
      • Contact: Penelope Madlala; Email: pmadlala@ecarefoundation.com
      • Principal Investigator: Sundrapragasen (Sandy) Pillay, MD
  • Central
    • George, Central, South Africa, 6529
      • Recruiting
      • TASK Applied Science - Eden
      • Contact: Suzanne Staples, MD; Phone Number: 044 873 3395; Email: s.staples@taskclinical.com
      • Contact: Amkelwa Dlunge; Email: a.dlunge@taskclinical.com
      • Principal Investigator: Suzanne Staples, MD
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2092
      • Recruiting
      • Clinical Research and HIV Research Unit (CHRU) @ Helen Joseph Hospital
      • Contact: Mohammed Rassool, MD; Phone Number: 112768800; Email: mrassool@witshealth.co.za
      • Contact: Betty Matome; Email: bmatome@witshealth.co.za
      • Principal Investigator: Mohammed Rassool, MD
    • Tembisa, Gauteng, South Africa, 1736
      • Not yet recruiting
      • The Aurum Institute Tembisa
      • Contact: Mmatsie Manentsa, MD; Phone Number: 27828214157; Email: mmanentsa@auruminstitute.org
      • Contact: Tebatso Matsepe; Email: tmatsepe@auruminstitute.org
      • Principal Investigator: Mmatsie Manentsa, MD
  • Gqeberha
    • Bethelsdorp, Gqeberha, South Africa, 6003
      • Recruiting
      • CHRU @ Isango Lethemba
      • Contact: Simone Faesen, MD; Phone Number: 27 41 811 0347; Email: Simfaesen@witshealth.co.za
      • Contact: Thuso Malatsi; Email: Tmalatsi@witshealth.co.za
      • Principal Investigator: Simone Faesen, MD
  • North West
    • Brits, North West, South Africa, 0250
      • Recruiting
      • Madibeng Centre for Research
      • Contact: Lindsey Faul, MD; Phone Number: +27 12 252 1140; Email: lfaul@madibengresearch.co.za
      • Contact: Ralinah Maepa; Email: rmaepa@madibengresearch.co.za
      • Principal Investigator: Lindsey Faul, MD
  • Soshangue
    • Pretoria, Soshangue, South Africa, 0152
      • Recruiting
      • Setshaba Research Center
      • Contact: Ntokozo Zuma-Gwala, MD; Phone Number: 073 476 1398; Email: NZuma-Gwala@setshaba.org.za
      • Contact: Mohammed Osman; Email: mosman@setshaba.org.za
      • Principal Investigator: Ntokozo Zuma-Gwala, MD
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • Recruiting
      • UCT Lung Institute
      • Principal Investigator: Rodney Dawson, MD
      • Contact: Rodney Dawson, MD; Phone Number: 27214067976; Email: rodney.dawson@uct.ac.za
      • Contact: Shanice Johnson; Email: shanice.johnson@uct.ac.za
    • Cape Town, Western Cape, South Africa, 7405
      • Recruiting
      • ONE MRI
      • Principal Investigator: Sandra Mukasa, MD
      • Contact: Sandra Mukasa, MD; Phone Number: 064 016 2837; Email: sandra.mukasa@onemri.co.za
      • Contact: Nosipho Mkuzangwe; Email: nosie.mkuzangwe@uct.ac.za
    • Cape Town, Western Cape, South Africa, 7405
      • Recruiting
      • TASK Applied Science - Brookylyn Chest Hospital
      • Contact: Fairoez Ryklief, MD; Phone Number: 021 510 2209; Email: dr.fairoez@task.org.za
      • Contact: Khomotso Zitha; Email: k.zitha@taskclinical.com
      • Principal Investigator: Fairoez Ryklief, MD
    • Cape Town, Western Cape, South Africa, 7505
      • Not yet recruiting
      • BioMedical Research Institute - Stellenbosch University @ Tygerberg Hospital
      • Contact: Andriette Hiemstra, MD; Phone Number: 021 938 9639; Email: ahiemstra@sun.ac.za
      • Contact: Bernadine Fransman; Email: bfransman@sun.ac.za
      • Principal Investigator: Andriette Hiemstra, MD
    • Cape Town, Western Cape, South Africa, 7750
      • Not yet recruiting
      • Desmond Tutu Health Foundation
      • Contact: Keren Middelkoop, MD; Phone Number: 717999262; Email: Keren.Middelkoop@hiv-research.org.za
      • Contact: Jabulisile Zuma; Email: Jabulisile.Zuma@hiv-research.org.za
      • Principal Investigator: Keren Middelkoop, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline and pretomanid	Drug: Bedaquiline, pretomanid and TBD09; Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 4 (30 participants): The combination of TBD09 (500 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
Experimental: Group 2; The combination of TBD09 (100 mg QD), bedaquiline and pretomanid	Drug: Bedaquiline, pretomanid and TBD09; Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 4 (30 participants): The combination of TBD09 (500 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
Experimental: Group 3; The combination of TBD09 (300 mg QD), bedaquiline and pretomanid	Drug: Bedaquiline, pretomanid and TBD09; Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 4 (30 participants): The combination of TBD09 (500 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
Experimental: Group 4; The combination of TBD09 (500 mg QD), bedaquiline and pretomanid	Drug: Bedaquiline, pretomanid and TBD09; Group 1 (30 participants): The combination of TBD09 (100 mg three times weekly, TIW), bedaquiline (200 mg daily, QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 2 (30 participants): The combination of TBD09 (100 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 3 (30 participants): The combination of TBD09 (300 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days; Drug: Bedaquiline, pretomanid and TBD09; Group 4 (30 participants): The combination of TBD09 (500 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days
Active Comparator: Group 5; The combination of linezolid (600 mg QD), bedaquiline and pretomanid	Drug: Bedaquiline, pretomanid and linezolid; Group 5 (30 participants): The combination of linezolid (600 mg QD), bedaquiline (200 mg QD), and pretomanid (200 mg QD), 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bactericidal Activity	Average daily change in MGIT sputum culture TTD from baseline to end-of-treatment (EOT)	From randomization through Day 28 (EOT)
Safety: SAEs	Proportion of participants with this event	Screening through Day 35 (EOS)
Safety: TEAEs	Proportion of participants with this event	Screening through Day 35 (EOS)
Safety: AESIs	Proportion of participants with this event	Screening through Day 35 (EOS)
Safety: AEs leading to treatment discontinuation	Proportion of participants with this event	Screening through Day 35 (EOS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Hematologic Effect	Proportion of participants who meet each of the following binary classifications of platelets, absolute neutrophil count (ANC), total white blood cell count (WBC), absolute lymphocyte count (ALC), and hemoglobin: Post-baseline result < lower limit of normal (LLN) among participants with baseline result > LLN (yes/no); Post-baseline result < 50% of LLN (yes/no); Post-baseline result ≥50% decrease relative to baseline (yes/no)	Randomization through Day 35 (EOS)
Safety: Visual Acuity Assessment	Proportion of participants with worsening of postbaseline visual acuity score of 2 lines or more in either eye using Snellen-type charts	Randomization through Day 35 (EOS)
Safety: Colour Vision Assessment	Proportion of participants with a new or worsening post-baseline color vision abnormality in either eye (by severity grade) using Ishihara plates	Randomization through Day 35 (EOS)
Safety: Brief Peripheral Neuropathy Screen (BPNS) score	Proportion of participants with a reported new or worsening post-baseline peripheral neuropathy symptom on BPNS in either lower extremity (overall and by severity grade)	Randomization through Day 35 (EOS)
Safety: Brief Peripheral Neuropathy Screen (BPNS) score	Proportion of participants with a new or worsening post-baseline peripheral neuropathy objective physical finding on BPNS in either lower extremity (overall and by severity grade)	Randomization through Day 35 (EOS)
Safety: Brief Peripheral Neuropathy Screen (BPNS) score	Proportion of participants with new or worsening post-baseline peripheral neuropathy as defined by new/worsening symptom and new/worsening objective physical finding on BPNS in the same lower extremity (overall and by severity grade).	Randomization through Day 35 (EOS)
Bactericidal activity	Proportion of participants with negative MGIT sputum cultures at D28	Day 28 (EOT)
Maximum plasma concentration (Cmax) of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 1 and Day 28
Time to maximum plasma concentration (Tmax) of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 1 and Day 28
Area under the curve from 0 to 24 hours (AUC0-24) of plasma concentration of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 1
Area under the curve from 0 to infinity (AUC0-inf) of plasma concentration of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 28
Area under the curve over the dosing interval on day 28 (AUCtau) of plasma concentration of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 28
Accumulation ratio (Area under the curve from 0 to the end of the dosing interval (AUCtau) / AUC0-24), Day 28 vs Day 1 of plasma concentration of TBD09	Concentrations of TBD09 administered in an investigational combination regimen.	Day 1 and Day 28

Collaborators and Investigators

• Sponsor: Gates Medical Research Institute
• Collaborators: IQVIA RDS Inc.
• Investigators: Study Director: Gates MRI, Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2026
• Primary Completion (Estimated): November 5, 2026
• Study Completion (Estimated): November 5, 2026

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pretomanid; linezolid; bedaquiline; TBD09; drug-susceptible pulmonary tuberculosis; oxazolidinone
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Oxazolidinones; Oxazoles; Linezolid; bedaquiline; pretomanid
• Other Study ID Numbers: Gates MRI-TBD09-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within 12 months of study completion date
• IPD Sharing Access Criteria: Anonymized participant-level data may be shared with the external research in accordance with trial participant' written and executed informed consent and applicable local regulations. Qualified research may submit a request along with a research proposal to Gates MRI for review. A data sharing agreement must be in place before any clinical trial data are shared. Additional restrictions may apply due to contractual obligations or regulatory constraints.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No