A Pan-TB Regimen Targeting Host and Microbe (panTB-HM)

May 22, 2025 updated by: The Aurum Institute NPC

A Novel 4-month Pan-TB Regimen Targeting Both Host and Microbe (panTB-HM)

This project will develop the first regimen meeting WHO criteria for a pan-TB indication, ie, not requiring knowledge of RIF susceptibility. The regimen will test sutezolid at 2 dose levels, with the approved anti-TB drugs bedaquiline and pretomanid, in a phase 2c trial. It will also test whether the addition of N-acetylcysteine (NAC), a re-purposed host-directed WHO essential medicine, can protect the lung and liver against oxidative damage, preserve lung function, and accelerate the eradication of MTB infection by replenishing glutathione (GSH).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
352

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Mozambique
      • Maputo, Mozambique
        • Instituto Nacional de Saúde
  • South Africa
      • Durban, South Africa, 4015
        • Clinical HIV Research Unit
      • Klerksdorp, South Africa, 2571
        • The Aurum Institute, Gavin J Churchyard Legacy Centre (Klerksdorp Clinical Research Centre)
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2092
        • Clinical HIV Research Unit
      • Tembisa, Gauteng, South Africa, 1632
        • The Aurum Institute: Tembisa Clinical Research Centre
    • North West Provice
      • Rustenburg, North West Provice, South Africa, 0299
        • The Aurum Institute, Rustenburg Clinical Research Centre
    • Western Cape
      • George, Western Cape, South Africa, 6529
        • TASK Eden
  • Tanzania
      • Mbeya, Tanzania
        • NIMR-Mbeya Medical Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged 18 to 65 years
  2. Willing and able to provide signed written consent prior to undertaking any trial-related procedures, or, in the case of illiteracy, witnessed oral consent
  3. Body weight (in light clothing without shoes) between 30 and 90 kg.
  4. Radiographic evidence of pulmonary tuberculosis
  5. Positive Xpert TB/RIF (original or Ultra) for MTB
  6. RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation
  7. If sexually active, willing to use an effective contraceptive method for the duration of tuberculosis treatment
  8. HIV-1 seronegative, or if HIV-1 seropositive, CD4 T cell count ≥100/µl and either receiving ART or willing to start ART during study participation
  9. SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer <0.8 ug/ml
  10. Willing to adhere to a diet excluding tyramine-rich foods (certain mold-ripened cheeses and cured meats), and to avoid eating grapefruits and pomelos

Exclusion Criteria:

  1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
  2. Current or imminent (within 24 hr) treatment for malaria.
  3. Pregnant or nursing
  4. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.
  5. TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
  6. History of allergy or hypersensitivity to any of the trial therapies or related substances.
  7. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
  8. Prior TB treatment in the preceding 6 months
  9. Angina pectoris requiring treatment with nitroglycerin or other nitrates
  10. Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator
  11. History of unstable Diabetes Mellitus requiring hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening.
  12. Use of systemic corticosteroids within the past 28 days.
  13. Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors
  14. Patients requiring treatment with antidepressants, including MAO inhibitors and SSRIs.

  15. Subjects with any of the following abnormal laboratory values:

    1. HBsAg positive
    2. creatinine >2 mg/dL
    3. hemoglobin <8 g/dL
    4. platelets <100x109 cells/L
    5. serum potassium <3.5 mM/L
    6. alanine aminotransferase (ALT) ≥2.0 x ULN
    7. alkaline phosphatase (AP) >5.0 x ULN
    8. total bilirubin >1.5 mg/dL
    9. random blood glucose >200 mg/dL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1 (S1200BP)
Sutezolid 1200mg QD plus bedaquiline and pretomanid for 4 months
Drug: Sutezolid
Sutezolid will be given at a dose of 1200mg QD in arm 1 and at a dose of 1600mg QD in arms 2 and 3.
Drug: Pretomanid
Pretomanid will be given at its approved dose
Drug: Bedaquiline
Bedaquiline will be given at its approved dose
Experimental: Arm 2 (S1600BP)
Sutezolid 1600mg QD plus bedaquiline and pretomanid for 4 months
Drug: Sutezolid
Sutezolid will be given at a dose of 1200mg QD in arm 1 and at a dose of 1600mg QD in arms 2 and 3.
Drug: Pretomanid
Pretomanid will be given at its approved dose
Drug: Bedaquiline
Bedaquiline will be given at its approved dose
Experimental: Arm 3 (S1600BPN)
Sutezolid 1600mg QD plus bedaquiline pretomanid and N-acetyl cysteine for 4 months
Drug: Sutezolid
Sutezolid will be given at a dose of 1200mg QD in arm 1 and at a dose of 1600mg QD in arms 2 and 3.
Drug: Pretomanid
Pretomanid will be given at its approved dose
Drug: Bedaquiline
Bedaquiline will be given at its approved dose
Drug: N-acetyl cysteine
NAC will be given at a dose of 1800 mg BID in arm 3
Other Names:
  • NAC
Active Comparator: Arm 4 (HRZE)
Rifafour (2HRZE/4HR)
Combination product: Rifafour
Fixed dose combination tablets for TB treatment will be given at approved doses

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The proportion of patients achieving durable (non-relapsing) cure
Time Frame: Assessed after 1 year of post-treatment follow-up
Assessed after 1 year of post-treatment follow-up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
The proportion of subjects with TE ALT increases, graded according to severity
Time Frame: From day 1 through 4 weeks post end-of-treatment
From day 1 through 4 weeks post end-of-treatment
The proportion of subjects with TE increases in transaminases and bilirubin meeting Hy's criteria for serious liver injury
Time Frame: From day 1 through 4 weeks post end-of-treatment
From day 1 through 4 weeks post end-of-treatment
The proportion of subjects with TE AEs, according to seriousness
Time Frame: From day 1 through 4 weeks post end-of-treatment
From day 1 through 4 weeks post end-of-treatment
The number of TE AEs per treatment arm, according to seriousness
Time Frame: From day 1 through 4 weeks post end-of-treatment
From day 1 through 4 weeks post end-of-treatment
The proportion of subjects requiring temporary or permanent treatment discontinuation due to safety or tolerability concerns
Time Frame: From day 1 through 4 weeks post end-of-treatment
From day 1 through 4 weeks post end-of-treatment
FEV1 and FVC at 1, 2, 6, and 18 months after initiation of treatment
Time Frame: 1, 2, 6, and 18 months after initiation of treatment
1, 2, 6, and 18 months after initiation of treatment
FEV1 and FVC slope during 6 and 18 months after initiation of treatment
Time Frame: 6 and 18 months after initiation of treatment
6 and 18 months after initiation of treatment
FEV1/FVC ratio at 1, 2, 6, and 18 months after initiation of treatment
Time Frame: 1, 2, 6, and 18 months after initiation of treatment
1, 2, 6, and 18 months after initiation of treatment
The proportion of subjects with sputum cultures showing growth of MTB at 1, 2, 3, and 4 months after initiation of treatment
Time Frame: 1, 2, 3, and 4 months after initiation of treatment
1, 2, 3, and 4 months after initiation of treatment
The hazard ratio for stable culture conversion through the 4th month of treatment
Time Frame: through the 4th month of treatment
through the 4th month of treatment
The proportion of subjects with treatment failure
Time Frame: More than 1 specimen showing growth of MTB during the final 6 weeks of treatment
More than 1 specimen showing growth of MTB during the final 6 weeks of treatment
The proportion of subjects with relapse
Time Frame: At week 72 for the control arm and at week 64 for the experimental arms
At week 72 for the control arm and at week 64 for the experimental arms

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
The proportion of subjects with non-TB cardiac or pulmonary AEs during the 18 months after TB diagnosis, according to seriousness.
Time Frame: During the 18 months after TB diagnosis
During the 18 months after TB diagnosis
The plasma concentration (AUC) of sutezolid and its main metabolite
Time Frame: Month 1
Month 1
The plasma concentration (Cmax and Cmin) of sutezolid and its main metabolite
Time Frame: Month 1
Month 1
The plasma concentration (T>MIC) of sutezolid and its main metabolite
Time Frame: Month 1
Month 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Aurum Institute NPC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ludwig-Maximilians - University of Munich
Global Alliance for TB Drug Development
University of Stellenbosch
Instituto Nacional de Saúde, Mozambique
National Institute for Medical Research, Tanzania
Sequella, Inc.
Stichting Katholieke Universiteit
Wits Health Consortium (Pty) Ltd

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Professor Robert Wallis, MD, The Aurum Institute NPC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 28, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 17, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AUR1-1-312
  • 24206 (Registry Identifier: Pan African Clinical Trials Registry (PACTR))
  • 6986 (South African Clinical Trials Registry (SANCTR))
  • RIA2019AMR-2647 (Other Grant/Funding Number: EDCTP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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