Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis (SYNERGY)

A Phase 2, Randomised, Controlled, Multicentre Two-Part Trial Assessing the Safety and Efficacy of TBAJ-587 as Part of a Combination Regimen in Newly Diagnosed, Drug-Sensitive, Sputum-Positive Pulmonary Tuberculosis

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

Study Overview

• Status: Not yet recruiting
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: TBAJ-587 50 mg; Drug: Pretomanid 200mg; Drug: Linezolid 600Mg Tab; Drug: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination); Drug: BTZ-043 250 mg or 500 mg; Drug: Quabodepistat (Q) 30 mg; Drug: Ganfeborole 20 mg

Detailed Description

This is a phase 2, two-part, multicentre, open label, controlled, randomised clinical trial in adult participants with newly diagnosed, sputum-positive pulmonary DS-TB. The trial will be performed in two sequential parts, each part containing parallel treatment arms.

Part A: Participants will be randomly assigned to one of two TBAJ-587 experimental regimens (TBA-587PaL, 100 mg or 200mg dose) or the active SOC control arm (HRZE:). Data from Part A will inform dose selection for Part B.

Part B: Participants will be randomly assigned to one of three experimental regimens. The sequential design allows for an interim analysis (section 10.5) between Parts A and B to evaluate the safety and efficacy of lower and higher TBAJ-587 doses before progressing to Part B, where the selected dose will be used. TBAJ-587 may be replaced by a similar diarylquinolone compound if, based on the interim analysis - for scientific and/or safety reasons - determines that TBAJ-587 should not proceed into Part B. Should this occur, the protocol will be updated via submission of a formal protocol amendment.

The active control arm included in Part A provides an internal benchmark to confirm that study procedures, microbiological methods, and clinical conduct perform as expected. Data generated from the Part A control arm will therefore serve as the primary internal reference for interpretation of Part B results. Therefore, there is no control arm in Part B.

In addition, the bacteriological endpoints used in this study, including time to positivity (TTP) and related measures of early bactericidal activity, are well characterised for HRZE in the published literature. These established external data provide a robust contextual framework against which Part B outcomes can be interpreted, without the need for an additional concurrent control arm.

This approach limits unnecessary exposure of participants to standard therapy beyond what is required to establish study validity, while allowing efficient evaluation of the selected investigational regimen in Part B.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kim Nieuwenhout; Phone Number: 021 1003606; Email: regulatory@taskclinical.com
• Study Contact Backup: Name: Vani Govender; Phone Number: 021 831 6596; Email: v.govender@taskclinical.com

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7405
      • TASK Brooklyn
      • Contact: Fairoez Ryklief, MBBChB; Phone Number: 021 510 2209; Email: f.ryklief@taskclinical.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• To be eligible to participate in this trial, an individual must meet all the following criteria:

  1. Provide written informed consent.
  2. Male or female aged 18-65 (inclusive)

  3. Clinical evidence of active TB disease, meeting either or both of the following criteria:

     1. Symptoms consistent with pulmonary TB at screening AND/OR
     2. Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 15 days prior to screening.

  4. 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.
  5. Able to produce a spot sputum with a volume of at least 4 ml.
  6. Body weight within the range of 30 to 100 kgs and body mass index within the range of 15 to 40 kg/m2.
  7. Newly diagnosed and untreated for this episode of TB.

  8. Individuals with a history of TB may be enrolled in this trial if they meet the following criteria:

     1. had a good treatment response in the opinion of the investigator (previous TB symptoms improved sufficiently or resolved) AND
     2. completed their previous TB treatment AND
     3. received their last dose of treatment more than 6 months before trial treatment AND • remained clinically well after completing treatment for their previous TB.
  9. Willing to abstain from alcohol and tyramine containing foods for the treatment duration.
  10. Willing to comply with study visits, all study procedures and treatment observation.

Exclusion Criteria:

• An individual who meets any of the following criteria will be excluded from participation in this trial:

  1. 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).
  2. 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).
  3. Severe clinical pulmonary TB e.g. respiratory failure or complications, likely to require hospital admission in the opinion of the investigator.
  4. Poor general condition (Karnofsky score ≤50) OR where any delay in treatment cannot be tolerated in the opinion of the investigator.
  5. Active malignancy requiring systemic therapy, radiotherapy or palliative therapy.
  6. 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).
  7. Cardiac valve abnormalities identified on echocardiogram.
  8. History of vitiligo.
  9. 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.
  10. History of seizure(s).
  11. History of vascular aneurysm.
  12. Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities.
  13. History of optic neuritis.
  14. 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.
  15. Any current or recent use of amphetamines or methamphetamines evident on toxicity screen.
  16. Any other medically or socially significant condition (e.g. psychiatric illness, chronic diarrhoeal disease, metabolic condition, other cardiovascular disease not listed under criterion 6), that would, in the opinion of the investigator, compromise the participant's safety or outcome in the trial; or lead to poor compliance with study visits and protocol requirements; or compromise the interpretation of trial safety and efficacy endpoints.
  17. Women who are currently pregnant or breast-feeding.
  18. Women of childbearing potential (WOCBP) who have had sexual intercourse without contraception after last menses or within the last 3 weeks (whichever is later); or, if unwilling to disclose this information, unable to provide two negative pregnancy tests 8 days apart during the screening period and on day 1 prior to randomisation .
  19. WOCBP unwilling or unable to use appropriate non-user dependent contraception during the study intervention period and for at least 6 months after the last dose of study intervention; and unwilling to commit to refrain from donating eggs (ova, oocytes) for the purpose of reproduction during this period
  20. Men who are unwilling to use a condom during the study period and for at least 90 days after the last dose of study drug to prevent pregnancy, unless they have had a vasectomy; and are unwilling to commit to refrain from donating fresh unwashed semen.
  21. Known allergy to one or more of the study drugs.

  22. Taking a concomitant medication that has a known or predicted interaction with any of the study drugs to which the participant might be randomised

      The participant need not be excluded if:

      1. the concomitant medication can be stopped or replaced with an alternative non-interacting medication, if needed AND
      2. the investigator judges there to be no residual clinical risk to the participant after stopping the concomitant medication (taking into account the washout period of 5x the half-life of the concomitant medication and the duration of the effect of the interaction on levels of study medication).
  23. Taking a concomitant medication that is known to prolong the QTc interval. The participant need not be excluded if the concomitant medication can be stopped or replaced with an alternative medication, if needed, and the duration of the QTc prolongation is expected to resolve prior to dosing of study medication (taking into account the washout period of 5x the half-life of the concomitant medication).
  24. Treatment with any immunosuppressive drugs within the 2 weeks prior to screening (taking systemic corticosteroids for less than 5 consecutive days and stopped at or prior to screening is not an exclusion; topical or inhaled steroids that are taken at a dose below the threshold considered to have systemic immunosuppressive effects are not excluded).
  25. Participation in other clinical intervention trials with an investigational agent within 8 weeks prior to the first dosing day in this trial.
  26. 12-lead ECGs at screening or at baseline shows QTcF >450 ms (men) or >460 ms (women) calculated by Fridericia's formula; and/or any other clinically significant abnormality such as arrhythmia or ischaemia.

  27. Any of the following laboratory parameters at screening:

      1. Hemoglobin < 9 g/dl
      2. Platelet count < 100 x 109 cells/L
      3. Absolute neutrophil count <1 000 cells/μL
      4. eGFR <75 ml/min, calculated using race free CKD EPI 2021 eGFR normalised by body surface area through additional inclusion of weight AND height parameters (not excluded if corrected to above this level)
      5. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 3 times the upper limit of normal (ULN)
      6. Total bilirubin > 1.5 times the ULN
      7. Serum potassium <3.5 mmol/L (not excluded if corrected to above this level)
      8. Serum magnesium < 0.50mmol/L (not excluded if corrected to above this level)
      9. Serum calcium (corrected for albumin level) < 2.10 mmol/L (not excluded if corrected to above this level).
      10. HbA1C >8.0%
  28. Hepatitis B surface antigen positive (known, or on a test performed at screening), hepatitis A IgM and hepatitis C antibodies. (Participants with positive hepatitis C antibodies but negative PCR can be allowed in the trial)

  29. Human Immunodeficiency Virus (HIV) antibody positive (known, or on test performed at screening) unless ALL of the following conditions are met:

      1. Viral load (HIV-RNA) below 200 copies/mL on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days).
      2. CD4 count > 200 cells/mm3 on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days).
      3. The participant has been taking a regimen of dolutegravir (DTG), tenofovir (TFV) and lamivudine(3TC)/emtricitabine for at least 6 months prior to screening with good adherence.
  30. For Part B only: Participants unwilling or unable to disclose information regarding their last unprotected sexual intercourse (UPSI), or whose responses are considered unreliable or non-compliant by the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; TBAJ-587 100 mg OD plus Pa 200 mg OD plus L 600 mg OD for 8 weeks	Drug: TBAJ-587 50 mg; 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; Other Names: Pretomanid 200mg and Linezolid 600mg; Drug: Pretomanid 200mg; Pretomanid Tablet 200 mg 200 mg OD; Drug: Linezolid 600Mg Tab; 600 mg OD
Experimental: Arm 2; TBAJ-587 200 mg OD plus Pa 200 mg OD plus L 600 mg OD for 8 weeks	Drug: TBAJ-587 50 mg; 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; Other Names: Pretomanid 200mg and Linezolid 600mg; Drug: Pretomanid 200mg; Pretomanid Tablet 200 mg 200 mg OD; Drug: Linezolid 600Mg Tab; 600 mg OD
Active Comparator: Arm 3; 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); H 75 mg, R 150 mg, Z 400 mg, E 275 mg fixed dose combination
Experimental: Arm 4; TBAJ-587 selected dose OD plus Pa 200 mg OD plus T 1 000 mg OD for 8 weeks	Drug: TBAJ-587 50 mg; 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; Other Names: Pretomanid 200mg and Linezolid 600mg; Drug: Pretomanid 200mg; Pretomanid Tablet 200 mg 200 mg OD; Drug: BTZ-043 250 mg or 500 mg; 1 000 mg OD
Experimental: Arm 5; TBAJ-587 selected dose OD plus Pa 200 mg OD plus Q 30 mg OD for 8 weeks	Drug: TBAJ-587 50 mg; 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; Other Names: Pretomanid 200mg and Linezolid 600mg; Drug: Pretomanid 200mg; Pretomanid Tablet 200 mg 200 mg OD; Drug: Quabodepistat (Q) 30 mg; 30 mg OD
Experimental: Arm 6; 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; 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; Other Names: Pretomanid 200mg and Linezolid 600mg; Drug: Pretomanid 200mg; Pretomanid Tablet 200 mg 200 mg OD; Drug: Linezolid 600Mg Tab; 600 mg OD; Drug: Ganfeborole 20 mg; 20 mg OD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline to the end of treatment at 8 weeks
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.	At the end of treatment at 8 weeks
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.	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	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.	From enrollment through the final follow-up visit at Week 12
Percentage of Participants With Drug-Related Treatment-Emergent Adverse Events	A drug-related TEAE is a treatment-emergent adverse event assessed by the investigator as having a causal relationship to one or more study drugs. Participants experiencing one or more drug-related TEAEs will be counted once. Measured as percentage of participants.	From enrollment through the final follow-up visit at Week 12
Percentage of Participants With Serious Treatment-Emerent Adverse Events	A serious TEAE is a treatment-emergent adverse event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability or incapacity, causes a congenital anomaly or birth defect, or is considered another medically important event. Participants experiencing one or more serious TEAEs will be counted once. Measured as percentage of participants.	From enrollment through the final follow-up visit at Week 12
Percentage of Participants With Treatment-Emergent Adverse Events Leading to Treatment Discontinuation	Participants who permanently discontinue one or more study drugs because of a TEAE will be included in this measure. Participants experiencing more than one qualifying event will be counted once. Measured as a percentage of participants.	From enrollment through the final follow-up visit at Week 12
Percentage of Participants With Treatment-Emergent Adverse Events Leading to Death	Participants who die as a result of a TEAE will be included in this measure. Each participant will be counted once, regardless of the number of TEAEs contributing to the death. Measured as a percentage of participants.	From enrollment through the final follow-up visit at Week 12
Percentage of Participants With Adverse Events of Special Interest	Adverse events of special interest are protocol-defined events that require specific monitoring because of their potential clinical importance in relation to the study drugs. Participants experiencing one or more adverse events of special interest will be counted once. Measured as a percentage of participants.	From enrollment through the final follow-up visit at Week 12
Maximum Observed Plasma Concentration of Study Drugs and Their Metabolites	The maximum observed plasma concentration (Cmax) will be estimated using non-compartmental analysis for the applicable study drugs and metabolites in each treatment arm. These include TBAJ-587 and its metabolites M2, M3 and M12; pretomanid; linezolid; BTZ-043 and its metabolite M1; quabodepistat; and ganfeborole. No pharmacokinetic measurements will be performed in the HRZE control arm. Measured in ng/mL	At Day 15 and Week 8 for participants in Part A and at Day 15 for participants in Part B
Minimum Observed Plasma Concentration of Study Drugs and Their Metabolites	The minimum observed plasma concentration (Cmin) will be estimated using non-compartmental analysis for the applicable study drugs and metabolites in each treatment arm. These include TBAJ-587 and its metabolites M2, M3 and M12; pretomanid; linezolid; BTZ-043 and its metabolite M1; quabodepistat; and ganfeborole. No pharmacokinetic measurements will be performed in the HRZE control arm. Measured as ng/mL.	At Day 15 and Week 8 for participants in Part A and at Day 15 for participants in Part B
Time to Maximum Observed Plasma Concentration of Study Drugs and Their Metabolites	The time to maximum observed plasma concentration (Tmax) will be estimated using non-compartmental analysis for the applicable study drugs and metabolites in each treatment arm. These include TBAJ-587 and its metabolites M2, M3 and M12; pretomanid; linezolid; BTZ-043 and its metabolite M1; quabodepistat; and ganfeborole. No pharmacokinetic measurements will be performed in the HRZE control arm. Measured in hours.	At Day 15 and Week 8 for participants in Part A and at Day 15 for participants in Part B
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours for Study Drugs and Their Metabolites	The area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) will be estimated using non-compartmental analysis for the applicable study drugs and metabolites in each treatment arm. These include TBAJ-587 and its metabolites M2, M3 and M12; pretomanid; linezolid; BTZ-043 and its metabolite M1; quabodepistat; and ganfeborole. No pharmacokinetic measurements will be performed in the HRZE control arm. Measured as ng-h/mL	At Day 15 and Week 8 for participants in Part A and at Day 15 for participants in Part B

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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	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).	From baseline to the end of treatment at 8 weeks
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.	From baseline before the first dose of study treatment to Day 15
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.	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 applicable
Mycobacterium tuberculosis Isolates With Resistance-Associated Mutations Following a Fourfold or Greater MIC Increase	Whole-genome sequencing will be performed on post-baseline Mycobacterium tuberculosis isolates showing a fourfold or greater increase from baseline in the minimum inhibitory concentration of a study drug. Sequencing will assess mutations associated with resistance to study drugs. Results will be reported as the number of sequenced isolates in which one or more resistance-associated mutations are identified.	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 applicable
Association Between Individual Drug Exposure and Change in Log10-Transformed Sputum Culture Time to Positivity Through Week 8	Individual drug exposure will be estimated using pharmacokinetic samples collected at Day 15 and Week 8 in Part A and at Day 15 in Part B. Exposure-response modelling will assess the relationship between estimated drug exposure and the change in log10-transformed sputum culture time to positivity from baseline through Week 8. Increasing time to positivity indicates a reduction in viable mycobacterial load.	From baseline to the end of treatment at Week 8; pharmacokinetic exposure is assessed at Day 15 and Week 8 in Part A and at Day 15 in Part B

Collaborators and Investigators

• Sponsor: TASK Applied Science
• Investigators: Principal Investigator: Fairoez Ryklief, MBBChB, TASK Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): July 23, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: July 21, 2026
• First Submitted That Met QC Criteria: August 14, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Drug-Sensitive Tuberculosis; Sputum-Positive Tuberculosis
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Azoles; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Amides; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Pyrazines; Acetamides; Acetates; Oxazolidinones; Oxazoles; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Linezolid; Rifampin; Isoniazid; Pyrazinamide; pretomanid; 2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one
• Other Study ID Numbers: UNITE4TB-04 / SYNERGY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Plan not yet available
• IPD Sharing Time Frame: Immediately after publication.
• IPD Sharing Access Criteria: Not available yet
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No