Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis
ConditionTuberculosis, Pulmonary
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorTASK Applied Science
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provide written informed consent.
Male or female aged 18-65 (inclusive)
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.
Disqualifiers
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).
Known or suspected extra-thoracic TB, miliary TB or disseminated TB (in the judgement of the investigator; note uncomplicated pleural effusion occupying <50% of hemithorax or concomitant intra- or extra-thoracic lymphadenopathy are not exclusions).
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.
Trial design
Design model
Parallel
Treatments tested in this trial
TBAJ-587 50 mg
DrugTBAJ-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
Pretomanid 200mg
DrugPretomanid Tablet 200 mg 200 mg OD
Linezolid 600Mg Tab
Drug600 mg OD
BTZ-043 250 mg or 500 mg
Drug1 000 mg OD
HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination)
DrugH 75 mg, R 150 mg, Z 400 mg, E 275 mg fixed dose combination
Quabodepistat (Q) 30 mg
Drug30 mg OD
Ganfeborole 20 mg
Drug20 mg OD
Treatment groups
135 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: TBAJ-587 100 mg, Pretomanid, Linezolid (Arm 1)Experimental treatment 3 interventions
Group B: TBAJ-587 200 mg, Pretomanid, Linezolid (Arm 2)Experimental treatment 3 interventions
Group C: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (Arm 3)Active comparator 1 intervention
Group D: TBAJ-587, Pretomanid, BTZ-043 (Arm 4)Experimental treatment 3 interventions
Group E: TBAJ-587, Pretomanid, Quabodepistat (Arm 5)Experimental treatment 3 interventions
Group F: TBAJ-587, Pretomanid, Linezolid, Ganfeborole (Arm 6)Experimental treatment 4 interventions
Trial outcomes
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).
Time frame
From baseline to the end of treatment at 8 weeksSecondary outcomes
1
Time to Sustained Sputum Culture Conversion From Baseline Through Week 8
Sustained sputum culture conversion is defined as the first of two consecutive negative sputum cultures, with no subsequent positive culture. Time to conversion will be calculated from baseline to the date of the first negative culture that meets this definition. Measured in days.
Time frame
From baseline to the end of treatment at 8 weeks2
Percentage of Participants With Sustained Sputum Culture Conversion at Week 8
Sustained sputum culture conversion is defined as the first of two consecutive negative sputum cultures, with no subsequent positive culture. Participants who meet this definition by Week 8 will be included in the percentage. Measured as percentage of participants.
Time frame
At the end of treatment at 8 weeks3
Percentage of Participants With Treatment-Emergent Adverse Events
A treatment-emergent adverse event (TEAE) is an adverse event that begins or worsens after the participant receives the first dose of study treatment. Participants experiencing one or more TEAEs will be counted once. Measured as percentage of participants.
Time frame
From enrollment through the final follow-up visit at Week 124
Percentage of Participants With Treatment-Emergent Adverse Events by Maximum Severity Grade as Assessed by CTCAE Version 5.0
The severity of each TEAE will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grades range from 1 to 5: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening and Grade 5 is death. Participants will be summarized according to their maximum recorded severity grade. Measured as percentage of participants.
Time frame
From enrollment through the final follow-up visit at Week 12Other outcomes
1
Change in Sputum Mycobacterial Load Measured Using the Molecular Bacterial Load Assay From Baseline Through Week 8
The Molecular Bacterial Load Assay (MBLA) measures viable Mycobacterium tuberculosis in sputum by quantifying mycobacterial ribosomal RNA. Mycobacterial load will be expressed as estimated colony-forming units per millilitre (eCFU/mL). The model-estimated change in log10-transformed mycobacterial load from baseline through Week 8 will be reported for each treatment arm. A decrease indicates a reduction in viable mycobacterial load. Measured as change in log10(eCFU/mL).
Time frame
From baseline to the end of treatment at 8 weeks2
Change in Sputum Lipoarabinomannan Concentration Measured Using the PATHFAST TB LAM Ag Assay From Baseline Through Week 8
The PATHFAST TB LAM Ag assay will be used to quantify lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis cell wall, in sputum. LAM concentration will be measured in picograms per millilitre. The model-estimated change in log10-transformed sputum LAM concentration from baseline through Week 8 will be reported for each treatment arm. A decrease indicates a reduction in sputum LAM concentration. Measured as change in log10(pg/mL).
Time frame
From baseline to the end of treatment at 8 weeks3
Change From Baseline in the TB27 Host Blood Transcriptomic Signature Score at Day 15
The TB27 host transcriptomic signature will be measured in whole-blood samples collected at baseline and Day 15. The change in the TB27 signature score from baseline to Day 15 will be calculated for each participant. The TB27 signature is an RNA-based host-response marker intended to predict time to sputum culture conversion. Associations between changes in the TB27 signature score and microbiological markers will be analysed separately.
Time frame
From baseline before the first dose of study treatment to Day 154
Minimum Inhibitory Concentration of Investigational Medicinal Products Against Mycobacterium tuberculosis Through Week 8
The minimum inhibitory concentration (MIC), defined as the lowest concentration of a study drug that inhibits growth of Mycobacterium tuberculosis, will be determined for applicable investigational medicinal products using isolates collected at baseline and during treatment. MIC values will be compared across assessment time points. A fourfold or greater increase from the baseline MIC will be considered a significant MIC shift and will trigger further testing as specified in the protocol. Measured as µg/mL.
Time frame
From baseline before the first dose of study treatment to the end of treatment at Week 8, including the make-up or early-withdrawal visit where applicableSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: