Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis

NCT07773610 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: UNITE4TB-04 / SYNERGY
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

A phase 2, two-part, multicentre, open label, controlled, randomised clinical trial in adult participants with newly diagnosed, sputum-positive pulmonary drug-sensitive tuberculosis (DSTB). Assessing the Safety and Efficacy of TBAJ-587 as Part of a Combination Regimen in Newly Diagnosed, Drug-Sensitive, Sputum-Positive Pulmonary Tuberculosis

Conditions

Tuberculosis, Pulmonary

Keywords

Drug-Sensitive Tuberculosis; Sputum-Positive Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Rate of Change in Log10-Transformed Sputum Culture Time to Positivity From Baseline Through Week 8

  Time to positivity is the time, measured in hours, required for a sputum culture to produce a positive result indicating detectable growth of Mycobacterium tuberculosis. The rate of change in log10-transformed time to positivity will be estimated for each treatment arm. Increasing time to positivity indicates a reduction in the viable mycobacterial load in sputum. Measured as change in log10(days).

  From baseline to the end of treatment at 8 weeks

Secondary Outcomes (13)

• Time to Sustained Sputum Culture Conversion From Baseline Through Week 8

  From baseline to the end of treatment at 8 weeks

• Percentage of Participants With Sustained Sputum Culture Conversion at Week 8

  At the end of treatment at 8 weeks

• Percentage of Participants With Treatment-Emergent Adverse Events

  From enrollment through the final follow-up visit at Week 12

• Percentage of Participants With Treatment-Emergent Adverse Events by Maximum Severity Grade as Assessed by CTCAE Version 5.0

  From enrollment through the final follow-up visit at Week 12

• Percentage of Participants With Drug-Related Treatment-Emergent Adverse Events

  From enrollment through the final follow-up visit at Week 12

Other Outcomes (6)

• Change in Sputum Mycobacterial Load Measured Using the Molecular Bacterial Load Assay From Baseline Through Week 8

  From baseline to the end of treatment at 8 weeks

• Change in Sputum Lipoarabinomannan Concentration Measured Using the PATHFAST TB LAM Ag Assay From Baseline Through Week 8

  From baseline to the end of treatment at 8 weeks

• Change From Baseline in the TB27 Host Blood Transcriptomic Signature Score at Day 15

  From baseline before the first dose of study treatment to Day 15

Study Arms (6)

TBAJ-587 100 mg, Pretomanid, Linezolid (Arm 1)

EXPERIMENTAL

TBAJ-587 100 mg OD plus Pa 200 mg OD plus L 600 mg OD for 8 weeks

Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: Linezolid 600Mg Tab

TBAJ-587 200 mg, Pretomanid, Linezolid (Arm 2)

EXPERIMENTAL

TBAJ-587 200 mg OD plus Pa 200 mg OD plus L 600 mg OD for 8 weeks

Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: Linezolid 600Mg Tab

Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (Arm 3)

ACTIVE COMPARATOR

H 75 mg, R 150 mg, Z 400 mg, E 275 mg fixed dose combination, weight-based dosing for 8 weeks

Drug: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination)

TBAJ-587, Pretomanid, BTZ-043 (Arm 4)

EXPERIMENTAL

TBAJ-587 selected dose OD plus Pa 200 mg OD plus T 1 000 mg OD for 8 weeks

Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: BTZ-043 250 mg or 500 mg

TBAJ-587, Pretomanid, Quabodepistat (Arm 5)

EXPERIMENTAL

TBAJ-587 selected dose OD plus Pa 200 mg OD plus Q 30 mg OD for 8 weeks

Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: Quabodepistat (Q) 30 mg

TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6)

EXPERIMENTAL

TBAJ-587 selected dose OD plus Pa 200 mg OD plus G 20 mg OD plus L 600 mg OD for 8 weeks

Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: Linezolid 600Mg Tab; Drug: Ganfeborole 20 mg

Interventions

TBAJ-587 50 mg DRUG

TBAJ-587LD Tablet 50 mg 100 mg OD TBAJ-587HD Tablet 50 mg 200 mg OD TBAJ-587SD Tablet 50 mg Dose selected from Part A daily

Also known as: Pretomanid 200mg and Linezolid 600mg

TBAJ-587 100 mg, Pretomanid, Linezolid (Arm 1); TBAJ-587 200 mg, Pretomanid, Linezolid (Arm 2); TBAJ-587, Pretomanid, BTZ-043 (Arm 4); TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6); TBAJ-587, Pretomanid, Quabodepistat (Arm 5)

Pretomanid 200mg DRUG

Pretomanid Tablet 200 mg 200 mg OD

TBAJ-587 100 mg, Pretomanid, Linezolid (Arm 1); TBAJ-587 200 mg, Pretomanid, Linezolid (Arm 2); TBAJ-587, Pretomanid, BTZ-043 (Arm 4); TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6); TBAJ-587, Pretomanid, Quabodepistat (Arm 5)

Linezolid 600Mg Tab DRUG

600 mg OD

TBAJ-587 100 mg, Pretomanid, Linezolid (Arm 1); TBAJ-587 200 mg, Pretomanid, Linezolid (Arm 2); TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6)

BTZ-043 250 mg or 500 mg DRUG

1 000 mg OD

TBAJ-587, Pretomanid, BTZ-043 (Arm 4)

HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination) DRUG

H 75 mg, R 150 mg, Z 400 mg, E 275 mg fixed dose combination

Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (Arm 3)

Quabodepistat (Q) 30 mg DRUG

30 mg OD

TBAJ-587, Pretomanid, Quabodepistat (Arm 5)

Ganfeborole 20 mg DRUG

20 mg OD

TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this trial, an individual must meet all the following criteria:
• Provide written informed consent.
• Male or female aged 18-65 (inclusive)
• Clinical evidence of active TB disease, meeting either or both of the following criteria:
• Symptoms consistent with pulmonary TB at screening AND/OR
• Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 15 days prior to screening.
• At least one sputum specimen produced at screening tested on either of the following:
• Xpert MTB/XDR and Ultra with:
• positive for M. tb
• a semi-quantitative result of 'medium' (cycle threshold value of \>16-22) or 'high' (cycle threshold value of \>16-22) AND
• does not show rifampicin and/or isoniazid resistance. OR
• a. Sputum smear
• Sputum positive for tubercle bacilli (at least 1+ on the IUATLD/WHO scale on smear microscopy) AND o Sensitive to rifampicin and isoniazid by rapid sputum-based test.
• Able to produce a spot sputum with a volume of at least 4 ml.
• Body weight within the range of 30 to 100 kgs and body mass index within the range of 15 to 40 kg/m2.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this trial:
• Taken more than 1 daily dose of medication with anti-tuberculous activity during the 14 days prior to randomisation (isoniazid, rifampicin, pyrazinamide, ethambutol, linezolid, moxifloxacin, levofloxacin or amikacin).
• Severe clinical pulmonary TB e.g. respiratory failure or complications, likely to require hospital admission in the opinion of the investigator.
• Poor general condition (Karnofsky score ≤50) OR where any delay in treatment cannot be tolerated in the opinion of the investigator.
• Active malignancy requiring systemic therapy, radiotherapy or palliative therapy.
• History of myocardial infarction, coronary heart disease or congestive cardiac failure; long QT syndrome or clinically significant arrhythmias; pulmonary hypertension; any known congenital cardiac problems; family history of long QT syndrome or sudden death from unknown or cardiac related cause; uncontrolled arterial hypertension (not excluded if this is corrected prior to randomisation).
• Cardiac valve abnormalities identified on echocardiogram.
• History of vitiligo.
• History of, or ongoing, inflammatory skin disorder such as leprosy, eczema, psoriasis, lichen planus, or other skin rash that would, in the opinion of the investigator, compromise the participant's safety or outcome in the trial.
• History of seizure(s).
• History of vascular aneurysm.
• Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities.
• History of optic neuritis.
• Current alcohol or illicit drug use sufficient to compromise the safety of the participant or research staff or compromise adherence to study procedures, in the opinion of the investigator.
• Any current or recent use of amphetamines or methamphetamines evident on toxicity screen.

Sponsors & Collaborators

• TASK Applied Science: lead

Study Sites (1)

TASK Brooklyn

Cape Town, Western Cape, 7405, South Africa

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

pretomanid; Linezolid; 2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one; Rifampin; Isoniazid; Pyrazinamide

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Pyrazines

Study Officials

• Fairoez Ryklief, MBBChB

  TASK Clinical Trials

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kim Nieuwenhout

CONTACT

021 1003606; regulatory@taskclinical.com

Vani Govender

CONTACT

021 831 6596; v.govender@taskclinical.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The two parts will be performed sequentially, each part containing parallel treatment arms, with an interim analysis between the two parts: * Part A: Participants will be randomly assigned to one of two TBAJ-587 experimental treatment regimens (100 mg or 200mg dose) combined with pretomanid (Pa) and linezolid (L), or to the control standard-of-care (SOC) (isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE)). * Interim Analysis: Data from Part A will be reviewed and inform dose selection for Part B. * Part B: Participants will be randomly assigned to an experimental regimen containing the selected TBAJ-587 dose and pretomanid (Pa) plus either BTZ-043 (T), quabodepistat (Q) or ganfeborole (G) and linezolid (L).

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: August 19, 2026
• Study Start: September 25, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately after publication.
• Access Criteria: Not available yet

Locations

ZA (1)