A Pan-TB Regimen Targeting Host and Microbe

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

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05686356

Acronym

panTB-HM

Enrollment

352

Registered

2023-01-17

Start date

2023-07-28

Completion date

2026-01-31

Last updated

2025-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tuberculosis

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).

Interventions

DRUGSutezolid

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.

DRUGN-acetyl cysteine

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

DRUGPretomanid

Pretomanid will be given at its approved dose

DRUGBedaquiline

Bedaquiline will be given at its approved dose

COMBINATION_PRODUCTRifafour

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
The proportion of patients achieving durable (non-relapsing) cure	Assessed after 1 year of post-treatment follow-up

Secondary

Measure	Time frame
The hazard ratio for stable culture conversion through the 4th month of treatment	through the 4th month of treatment
The proportion of subjects with treatment failure	More than 1 specimen showing growth of MTB during the final 6 weeks of treatment
The proportion of subjects with relapse	At week 72 for the control arm and at week 64 for the experimental arms
The proportion of subjects with TE AEs, according to seriousness	From day 1 through 4 weeks post end-of-treatment
The number of TE AEs per treatment arm, according to seriousness	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	From day 1 through 4 weeks post end-of-treatment
FEV1 and FVC at 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	6 and 18 months after initiation of treatment
FEV1/FVC ratio at 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 TE ALT increases, graded according to severity	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	From day 1 through 4 weeks post end-of-treatment
The proportion of subjects with sputum cultures showing growth of MTB at 1, 2, 3, and 4 months after initiation of treatment	1, 2, 3, and 4 months after initiation of treatment

Other

Measure	Time frame
The proportion of subjects with non-TB cardiac or pulmonary AEs during the 18 months after TB diagnosis, according to seriousness.	During the 18 months after TB diagnosis
The plasma concentration (AUC) of sutezolid and its main metabolite	Month 1
The plasma concentration (Cmax and Cmin) of sutezolid and its main metabolite	Month 1
The plasma concentration (T>MIC) of sutezolid and its main metabolite	Month 1

Countries

Mozambique, South Africa, Tanzania

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 28, 2026