A Pan-TB Regimen Targeting Host and Microbe

NCT ID: NCT05686356

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-28
• Study Completion Date: 2026-01-31

Brief Summary

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).

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 (S1200BP)

Sutezolid 1200mg QD plus bedaquiline and pretomanid for 4 months

Group Type: EXPERIMENTAL

Sutezolid

Intervention Type: DRUG

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.

Pretomanid

Intervention Type: DRUG

Pretomanid will be given at its approved dose

Bedaquiline

Intervention Type: DRUG

Bedaquiline will be given at its approved dose

Arm 2 (S1600BP)

Sutezolid 1600mg QD plus bedaquiline and pretomanid for 4 months

Group Type: EXPERIMENTAL

Sutezolid

Intervention Type: DRUG

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.

Pretomanid

Intervention Type: DRUG

Pretomanid will be given at its approved dose

Bedaquiline

Intervention Type: DRUG

Bedaquiline will be given at its approved dose

Arm 3 (S1600BPN)

Sutezolid 1600mg QD plus bedaquiline pretomanid and N-acetyl cysteine for 4 months

Group Type: EXPERIMENTAL

Sutezolid

Intervention Type: DRUG

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.

N-acetyl cysteine

Intervention Type: DRUG

NAC will be given at a dose of 1800 mg BID in arm 3

Pretomanid

Intervention Type: DRUG

Pretomanid will be given at its approved dose

Bedaquiline

Intervention Type: DRUG

Bedaquiline will be given at its approved dose

Arm 4 (HRZE)

Rifafour (2HRZE/4HR)

Group Type: ACTIVE_COMPARATOR

Rifafour

Intervention Type: COMBINATION_PRODUCT

Fixed dose combination tablets for TB treatment will be given at approved doses

Interventions

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.

Intervention Type: DRUG

N-acetyl cysteine

NAC will be given at a dose of 1800 mg BID in arm 3

Intervention Type: DRUG

Pretomanid

Pretomanid will be given at its approved dose

Intervention Type: DRUG

Bedaquiline

Bedaquiline will be given at its approved dose

Intervention Type: DRUG

Rifafour

Fixed dose combination tablets for TB treatment will be given at approved doses

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

NAC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

Stichting Katholieke Universiteit

OTHER

Sponsor Role: collaborator

Wits Health Consortium (Pty) Ltd

OTHER

Sponsor Role: collaborator

Instituto Nacional de Saúde, Mozambique

OTHER_GOV

Sponsor Role: collaborator

National Institute for Medical Research, Tanzania

OTHER_GOV

Sponsor Role: collaborator

University of Stellenbosch

OTHER

Sponsor Role: collaborator

Sequella, Inc.

INDUSTRY

Sponsor Role: collaborator

Global Alliance for TB Drug Development

OTHER

Sponsor Role: collaborator

The Aurum Institute NPC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor Robert Wallis, MD

Role: PRINCIPAL_INVESTIGATOR

The Aurum Institute NPC

Locations

Instituto Nacional de Saúde

Maputo, , Mozambique

Clinical HIV Research Unit

Durban, Durban, South Africa

Clinical HIV Research Unit

Johannesburg, Gauteng, South Africa

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, Gauteng, South Africa

The Aurum Institute, Gavin J Churchyard Legacy Centre (Klerksdorp Clinical Research Centre)

Klerksdorp, Klerksdorp, South Africa

The Aurum Institute, Rustenburg Clinical Research Centre

Rustenburg, North West Provice, South Africa

TASK Eden

George, Western Cape, South Africa

NIMR-Mbeya Medical Research Centre

Mbeya, , Tanzania

Countries

Mozambique; South Africa; Tanzania

Other Identifiers

24206

Identifier Type: REGISTRY

Identifier Source: secondary_id

6986

Identifier Type: REGISTRY

Identifier Source: secondary_id

RIA2019AMR-2647

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AUR1-1-312

Identifier Type: -

Identifier Source: org_study_id