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RecruitingNCT06114628PARADIGM4TBUpdated Oct 15, 2026

Platform Assessing Regimens and Durations In a Global Multisite Consortium for TB

A Phase 2 interventional study of Ganfeborole and BTZ-043 in Pulmonary Tuberculosis, sponsored by University College, London. Recruiting at 11 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-15.

Sponsored by University College, London · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Jan 2024; still recruiting 2 years 10 months later.
Updated Oct 15, 2026Sponsor changedGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
2,500
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The UNITE4TB consortium is a group of universities and pharmaceutical companies funded by the European Union. This consortium are carrying out a trial to find better and faster ways to treat tuberculosis (TB). The standard treatment for TB takes 24 weeks and uses four drugs. The consortium want to find new treatments that are faster but just as safe and effective.

In the trial, two new drugs will be used, BTZ-043 and GSK3036656, along with the drugs that are already used to treat TB in a variety of combinations (11 different combinations initially). These new drugs have worked well in tests with animals and have reduced the amount of TB bacteria in people's sputum/phlegm when used alone for two weeks. These new drugs will be used in combination with other TB drugs for a longer time (up to 16 weeks) in people with TB. The UNITE4TB consortium want to see if they work well and are safe.

This trial will take place at sites across the world and will involve people with TB of the lungs that would usually respond well to the standard treatment. But the new treatments being tested might also work for people with drug resistant TB, that's harder to treat.

The trial has two parts. In the first part, different combinations of drugs will be tried on up to 700 people for 16 weeks. These combinations will be compared to the standard 24-week treatment to see which ones work the best and are safe.

In the second part, the best combinations from the first part will be taken to try to find out what the best length of time is to give the treatment for. These combinations will be tried on up to 1800 people giving them either 8, 10, 12, 14 or 16 weeks treatment. The investigators will follow these people for a total of 72 weeks to make sure the treatment is working.

The UNITE4TB consortium hope that this trial will find new treatments that are fast, safe, and effective for both regular TB and resistant TB. If it works, it can then be tested again in a bigger trial to be sure.

Read the detailed description

Study Design:

This will be a randomised, open-label, multicentre, seamless phase 2B (regimen selection) and 2C (duration randomisation), multi-arm multi-stage, platform clinical trial

Overall objective:

The overall objective is to identify novel drug regimen(s) with acceptable safety profile, non-inferior efficacy, and shortened treatment duration compared to the standard-of-care 24-week HRZE/HR regimen (isoniazid + rifampicin + pyrazinamide + ethambutol for 8 weeks then isoniazid + rifampicin for 16 weeks) that could be used to treat both rifampicin-susceptible and resistant TB.

Specific sub-objectives:

The objective of the Phase 2B stage is to identify novel regimens of 16 weeks' duration with acceptable safety profile and the greatest potential, based on assessment of quantitative sputum liquid culture and treatment failure/relapse, to progress to investigation of optimal treatment duration

Amongst the regimens selected for progression from phase 2B to phase 2C stage, the objective is then to further evaluate the safety profile of these regimens and to identify the optimal treatment duration (between 8 and 16 weeks) based on unfavourable outcome to support advancement to future Phase 3 trials.

Setting:

Specialist TB clinics and research centres in sites across Europe, Asia, Africa and South America

Population:

Adults with newly diagnosed, rifampicin-susceptible pulmonary TB

Duration:

Individual participant participation will be for 72 weeks. The total duration of trial is 5 years.

Interventions:

Phase 2B: Participants will be randomised (1:1:1..1) to the following 12 arms (A-L) initially. Additional arms maybe added through protocol amendment.

Control, standard-of-care regimen, given for 24 weeks

A. Isoniazid + rifampicin + pyrazinamide + ethambutol for 8 weeks then isoniazid + rifampicin for 16 weeks

Novel treatment regimens each given for 16 weeks

B. Bedaquiline + delamanid + moxifloxacin

C. Bedaquiline + delamanid + moxifloxacin + GSK306656

D. Bedaquiline + delamanid + pyrazinamide + GSK306656

E. Bedaquiline + delamanid + linezolid (for first 8 weeks) + GSK306656

F. Bedaquiline + pretomanid + moxifloxacin + GSK306656

G. Bedaquiline + delamanid + moxifloxacin + BTZ-043

H. Bedaquiline + delamanid + pyrazinamide + BTZ-043

I. Bedaquiline + delamanid + linezolid (for first 8 weeks) + BTZ-043

J. Bedaquiline + pretomanid + moxifloxacin + BTZ-043

K. Bedaquiline + moxifloxacin + pyrazinamide + BTZ-043

L. Bedaquiline + delamanid + GSK306656 + BTZ-043

and in a second wave of recruitment, the following:

M. Bedaquiline + delamanid + moxifloxacin +quabodepistat

N. Bedaquiline + pretomanid + moxifloxacin + quabodepistat

O. Bedaquiline + delamanid + ganfeborole + quabodepistat

Q. Bedaquiline + pretomanid + delpazolid + BTZ-043

There are two planned interim analyses of safety and efficacy data by an Independent Data Monitoring Committee in Phase 2B. The first interim analysis will occur when the last participant for arms to be included in the analysis, completes 16 weeks of treatment and all necessary data are available. The second interim analysis will occur when the last participant for arms to be included in the analysis completes to week 48 (from randomisation) and all necessary data are available. The IDMC will make recommendation to the Trial Steering Committee (TSC) and Asset Holders on the progression of regimens to Phase 2C. The TSC will make the final decision. Arm B (bedaquiline + delamanid + moxifloxacin) will not be considered for progression to 2C.

Phase 2C:

For regimens selected for progression (following interim phase 2B evaluation). Participants will be randomised to treatment durations of either 8 weeks, 10 weeks, 12 weeks, 14 weeks, 16 weeks or to the 24-week standard-of-care regimen (as described above).

Primary Efficacy Outcome Measure(s) -

Phase 2B: rate of change in log10(TTP) over 0 to 12 weeks, where TTP is time to positivity measured in days from MGIT culture

Phase 2C: Favourable/unfavourable status (binary) at week 48 from randomisation

Safety Outcome Measures (Phase 2B and 2C) -

The following outcomes will be reported up to week 26 from randomisation (unless otherwise stated):

  • Grade 3/4/5 adverse events (DAIDS grading scale)
  • Serious Adverse Events
  • Adverse Events of Special Interest
  • Regimen-related adverse events leading to withdrawal from the study
  • Adverse events leading to discontinuation of the regimen

Number of Participants to be Studied:

Up to 2500 overall - 700 in phase 2B and 1800 in phase 2C (distribution between phases depends on progression according to specified decision-making steps)

02

Conditions studied

  • Pulmonary Tuberculosis
03

In context

Tuberculosis, Pulmonary

319 studies on the registry are indexed under Tuberculosis, Pulmonary; 71 are open to participants now.

This study's planned enrollment of 2,500 is above the median of 146 across 227 interventional studies indexed under Tuberculosis, Pulmonary.

Browse Tuberculosis, Pulmonary studies →

Lead sponsor

University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.

Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.

Browse University College, London studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Age 18 years or above at screening (or above age of legal consent at screening, if this is higher than 18 years in the jurisdiction in which the study is taking place)

  2. 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 7 days prior to screening

  3. At least one sputum specimen produced at screening tested on Xpert MTB/RIF Ultra that has:

    • a semi-quantitative result of 'medium' or 'high' AND
    • does not show rifampicin resistance
  4. Body weight within the range of 30 to 100kg and within the range of 15 to 40kg/m2
  5. Willing to comply with study visits, all study procedures and treatment observation
  6. Resident at a fixed address that is readily accessible for visiting, within feasible travelling distance to the site and likely to remain resident there for the duration of trial follow-up
  7. Has provided written

Exclusion criteria

Exclusion Criteria:

  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) (for Phase 2b and Phase 2c)
  2. Known isoniazid resistance (at sites where national isoniazid monoresistance is greater than 10% rapid testing at screening is mandated; at other sites rapid testing at screening is optional)
  3. 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)
  4. Severe clinical pulmonary TB e.g. respiratory failure or complications likely to require hospital admission in the opinion of the investigator
  5. Poor general condition ( score ≤50) OR where any delay in treatment cannot be tolerated in the opinion of the investigator
  6. Active requiring systemic therapy, radiotherapy or palliative therapy
  7. History of myocardial infarction, coronary heart disease or congestive cardiac failure; long syndrome or 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)
  8. Vitiligo
  9. History of seizure(s)
  10. Current tendinitis (any cause) or history of tendinopathy associated with fluoroquinolone use
  11. History of vascular aneurysm
  12. Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities
  13. 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
  14. Any current or recent use of amphetamines or methamphetamines, either reported or evident on toxicity screen, if performed
  15. Any other medically or socially significant condition (e.g. psychiatric illness, chronic diarrhoeal disease, metabolic condition, other cardiovascular disease not listed under criterion 7), 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
  16. Women who are currently pregnant or breast-feeding
  17. Women of unwilling or unable to use appropriate effective during the study intervention period and for at least 14 days 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; definitions of childbearing potential and appropriate effective contraception given below**
  18. 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 during any activity that allows for the passage of ejaculate to another person; and are unwilling to commit to refrain from donating fresh unwashed semen
  19. Known allergy to one or more of the study drugs

  20. 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 of 5x the half-life of the concomitant medication and the duration of the effect of the interaction on levels of study medication)
  21. 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)
  22. Treatment with any drugs within the 2 weeks prior to screening (taking systemic for less than 5 consecutive days and stopped at or prior to screening are 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)
  23. Participation in other clinical intervention trial with an agent within 8 weeks prior to the first dosing day in this trial
  24. 12-lead ECGs at screening or at baseline shows QTcF >450ms (men) or >460ms (women) calculated by Fridericia's formula; and/or any other clinically significant abnormality such as arrhythmia or ischaemia

  25. Any of the following laboratory parameters at screening:

    1. \< 9g/dl
    2. count \< 50 x 109 cells/L
    3. \<1000 cells/μL
    4. of \<75ml/min, calculated using Cockcroft-Gault equation*
    5. or AST > 3 times the
    6. Total > 1.5 times upper limit of normal
    7. Serum potassium \<3.5 mmol/L (not excluded if corrected to above this level)
    8. Serum magnesium \< 0.70mmol/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)
  26. surface antigen positive (known, or on a test performed at screening)
  27. antibody positive (known, or on test performed at screening)*
  28. Known virus infection (unless also known to have negative PCR test)*
Terms in these criteria, in plain language(22)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Washout period

A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
2,500 participants (estimated)

Study arms

  • Active comparator
    A. Standard TB Regimen. 2HRZE/4HR

    24 weeks treatment in both Phase 2B and 2C - 8 weeks Rifampicin, Isoniazid, Pyrazinamide, Ethambutol followed by 16 weeks Rifampicin and Isoniazid.

    Drug: Pyrazinamide (Z) · Drug: Rifampicin (R) · Drug: Isoniazid (H) · Drug: Ethambutol (E)

  • Experimental
    Arm B. BDM

    Bedaquiline, Delamanid, Moxifloxacin for 16 weeks in Phase 2B

    Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Moxifloxacin (M)

  • Experimental
    Arm C. BDM + Gan

    Bedaquiline, Delamanid, Moxifloxacin and Ganfeborole for 16 weeks in Phase 2B Bedaquiline, Delamanid, Moxifloxacin and Ganfeborole for 8-16 weeks in phase 2C

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Moxifloxacin (M)

  • Experimental
    Arm D. BDZ + Gan

    Bedaquiline, Delamanid, Pyrazinamide and Ganfeborole for 16 weeks in Phase 2B Bedaquiline, Delamanid, Pyrazinamide and Ganfeborole for 8-16 weeks in phase 2C

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Pyrazinamide (Z)

  • Experimental
    Arm E. BDL + 656

    Bedaquiline, Delamanid, Linezolid and Ganfeborole for 8 weeks followed by 8 weeks Bedaquiline, Delamanid and Ganfeborole in Phase 2B Bedaquiline, Delamanid, Linezolid and Ganfeborole for 8 weeks followed by 0-8 weeks Bedaquiline, Delamanid and Ganfeborole in Phase 2C

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Linezolid (L)

  • Experimental
    Arm F. BPaM + Gan

    Bedaquiline, Pretomanid, Moxifloxacin and Ganfeborole for 16 weeks in Phase 2B Bedaquiline, Pretomanid, Moxifloxacin and Ganfeborolefor 8-16 weeks in Phase 2C

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Pretomanid (Pa) · Drug: Moxifloxacin (M)

  • Experimental
    Arm G. BDM + BTZ-043

    Bedaquiline, Delamanid, Moxifloxacin and BTZ-043 for 16 weeks in Phase 2B Bedaquiline, Delamanid, Moxifloxacin and BTZ-043 for 8-16 weeks in phase 2C

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Moxifloxacin (M)

  • Experimental
    Arm H. BDZ + BTZ-043

    Bedaquiline, Delamanid, Pyrazinamide and BTZ-043 for 16 weeks in Phase 2B Bedaquiline, Delamanid, Pyrazinamide and BTZ-043 for 8-16 weeks in phase 2C

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Pyrazinamide (Z)

  • Experimental
    Arm I. BDL + BTZ-043

    Bedaquiline, Delamanid, Linezolid and BTZ-043 for 8 weeks followed by 8 weeks Bedaquiline, Delamanid and BTZ-043 in Phase 2B Bedaquiline, Delamanid, Linezolid and BTZ-043 for 8 weeks followed by 0-8 weeks Bedaquiline, Delamanid and BTZ-043 in Phase 2C

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Linezolid (L)

  • Experimental
    Arm J. BPaM + BTZ-043

    Bedaquiline, Pretomanid, Moxifloxacin and BTZ-043 for 16 weeks in Phase 2B Bedaquiline, Pretomanid, Moxifloxacin and BTZ-043 for 8-16 weeks in Phase 2C

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Pretomanid (Pa) · Drug: Moxifloxacin (M)

  • Experimental
    Arm K. BMZ + BTZ-043

    Bedaquiline, Moxifloxacin, Pyrazinamide and BTZ-043 for 16 weeks in Phase 2B Bedaquiline, Moxifloxacin, Pyrazinamide and BTZ-043 for 8-16 weeks in phase 2C

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Moxifloxacin (M) · Drug: Pyrazinamide (Z)

  • Experimental
    Arm L. BD + Gan + BTZ-043

    Bedaquiline, Delamanid, Ganfeborole and BTZ-043 for 16 weeks in Phase 2B Bedaquiline, Delamanid, Ganfeborole and BTZ-043 for 8-16 weeks in phase 2C

    Drug: Ganfeborole · Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Delamanid (D)

  • Experimental
    Arm M: BDM + Q

    Bedaquiline, delamanid, moxifloxacin, quabodepistat for 16 weeks in Phase 2B

    Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Moxifloxacin (M) · Drug: Quabodepistat (Q)

  • Experimental
    Arm N: BPAM + Q

    Bedaquiline, pretomanid, moxifloxacin, quabodepistat for 16 weeks in Phase 2B

    Drug: Bedaquiline (B) · Drug: Pretomanid (Pa) · Drug: Moxifloxacin (M) · Drug: Quabodepistat (Q)

  • Experimental
    Arm O: BD + Gan + Q

    Bedaquiline, delamanid, ganfeborole, quabodepistat for 16 weeks in Phase 2B

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Delamanid (D) · Drug: Quabodepistat (Q)

  • Experimental
    Arm P: BPa + Gan +Q

    Bedaquiline, pretomanid, ganfeborole, quabodepistat for 16 weeks in Phase 2B

    Drug: Ganfeborole · Drug: Bedaquiline (B) · Drug: Pretomanid (Pa) · Drug: Quabodepistat (Q)

  • Experimental
    Arm Q: BPa + DZD + BTZ-043

    Bedaquiline, pretomanid, delpazolid, BTZ-043 for 16 weeks in Phase 2B

    Drug: BTZ-043 · Drug: Bedaquiline (B) · Drug: Pretomanid (Pa) · Drug: Delpazolid (DZD)

Interventions

06

What researchers measure

Primary outcomes

  1. Rate of change in log10(Time to Positivity of MGIT culture) (Phase 2B)

    Primary Efficacy Outcome in Phase 2B, rate of change in log10(Time to positivity)

    Time frame: Over 0-12 weeks

  2. Favourable/Unfavourable outcome (Phase 2C)

    Primary Efficacy Outcome in Phase 2C, the proportion of participants with a favourable outcome status

    Time frame: at 48 weeks from randomisation

Secondary outcomes

  1. Grade 3/4/5 adverse events (Phase 2B)

    Safety outcome in Phase 2B, grade 3/4/5 adverse events

    Time frame: Up to 26 weeks from randomisation

  2. Grade 3/4/5 adverse events (Phase 2C)

    Safety outcome in Phase 2C, grade 3/4/5 adverse events

    Time frame: Up to 26 weeks from randomisation

  3. Serious adverse events (Phase 2B)

    Safety outcome in Phase 2B, serious adverse events

    Time frame: Up to 26 weeks from randomisation

  4. Serious adverse events (Phase 2C)

    Safety outcome in Phase 2C, serious adverse events

    Time frame: Up to 26 weeks from randomisation

  5. Adverse events of special interest (Phase 2B)

    Safety outcome in Phase 2B, adverse events of special interest

    Time frame: Up to 26 weeks from randomisation

  6. Adverse events of special interest (Phase 2C)

    Safety outcome in Phase 2C, adverse events of special interest

    Time frame: Up to 26 weeks from randomisation

  7. Regimen-related adverse events (Phase 2B)

    Safety outcome in Phase 2B, Regimen-related adverse events

    Time frame: Up to 26 weeks from randomisation

  8. Regimen-related adverse events (Phase 2C)

    Safety outcome in Phase 2C, Regimen-related adverse events

    Time frame: Up to 26 weeks from randomisation

  9. Adverse events leading to withdrawal from the study (Phase 2B)

    Safety outcome in Phase 2B, Adverse events leading to withdrawal from the study

    Time frame: Up to 26 weeks from randomisation

  10. Adverse events leading to withdrawal from the study (Phase 2C)

    Safety outcome in Phase 2C, Adverse events leading to withdrawal from the study

    Time frame: Up to 26 weeks from randomisation

  11. Adverse events leading to discontinuation of the regimen (AESI) (Phase 2B)

    Safety outcome in Phase 2B, Adverse events leading to discontinuation of the regimen

    Time frame: Up to 26 weeks from randomisation

  12. Adverse events leading to discontinuation of the regimen (Phase 2C)

    Safety outcome in Phase 2C, Adverse events leading to discontinuation of the regimen

    Time frame: Up to 26 weeks from randomisation

  13. Favourable/unfavourable status (Phase 2B)

    Secondary Efficacy Outcome in Phase 2B, the proportion of participants with a favourable outcome status

    Time frame: At week 48

  14. Favourable/unfavourable status (Phase 2B)

    Secondary Efficacy Outcome in Phase 2B and 2C, the proportion of participants with a favourable outcome status

    Time frame: At week 72

  15. Favourable/unfavourable status (Phase 2C)

    Secondary Efficacy Outcome in Phase 2B and 2C, the proportion of participants with a favourable outcome status

    Time frame: At week 72

  16. Time to culture negative status (Phase 2B)

    Secondary Efficacy Outcome in Phase 2B, time to culture negative status

    Time frame: 0-24 weeks

  17. Time to culture negative status (Phase 2C)

    Secondary Efficacy Outcome in Phase 2C, time to culture negative status

    Time frame: 0-24 weeks

  18. Culture conversion measured from Mycobacterial Growth Indicator Tube system (MGIT) liquid culture results (Phase 2B)

    Secondary Efficacy Outcome in Phase 2B, culture conversion status

    Time frame: weeks 4, 8, 12 and 16

  19. Culture conversion measured from Mycobacterial Growth Indicator Tube system (MGIT) liquid culture results (Phase 2C)

    Secondary Efficacy Outcome in Phase 2C, culture conversion status

    Time frame: weeks 4, 8, 12 and 16

  20. PK parameters; Area under the plasma concentration versus time curve (AUC) over 0 to 24 hours

    Pharmacokinetic (PK) Outcomes; Area under the plasma concentration versus time curve (AUC) over 0 to 24 hours

    Time frame: weeks 4 and 8

  21. PK parameters; Peak Plasma Concentration (CMax)

    Pharmacokinetic (PK) Outcomes; Peak Plasma Concentration (CMax)

    Time frame: weeks 4 and 8

07

Study locations

8 of 11 sites recruiting
  • PMSI Institute of Pneumology "Chiril Draganiuc"
    Chisinau, Moldova
    Active, not recruiting

    Not enrolling at this site.

  • TASK Brooklyn
    Cape Town, South Africa
    Recruiting
    • Fairoez Ryklief · Contact
  • University of Cape Town Lung Institute
    Cape Town, South Africa
    Recruiting
    • Rodney Dawson · Contact
  • TASK Eden
    George, South Africa
    Recruiting
    • Louis Botha · Contact
  • NIMR Mbeya
    Mbeya, Tanzania
    Recruiting
    • Lilian Tina Minja · Contact
  • Kibong'oto Infectious Diseases Hospital
    Moshi, Tanzania
    Recruiting
    • Stellah Mpagama · Contact
  • NIMR Mwanza
    Mwanza, Tanzania
    Recruiting
    • Kidola Jeremiah · Contact
  • Joint Clinical Research Centre
    Kampala, Uganda
    Recruiting
    • Cissy Kityo Mutuluuza · Contact
  • Makerere University Lung Institute
    Kampala, Uganda
    Recruiting
    • Bruce Kirenga · Contact
  • National Lung Hospital
    Hanoi, Vietnam
    Active, not recruiting

    Not enrolling at this site.

  • Pnth/Oucru
    Ho Chi Minh City, Vietnam
    Active, not recruiting

    Not enrolling at this site.

08

References and documents

Publications

  • Eckhardt E, Li Y, Mamerow S, Schinkothe J, Sehl-Ewert J, Dreisbach J, Corleis B, Dorhoi A, Teifke J, Menge C, Kloss F, Bastian M. Pharmacokinetics and Efficacy of the Benzothiazinone BTZ-043 against Tuberculous Mycobacteria inside Granulomas in the Guinea Pig Model. Antimicrob Agents Chemother. 2023 Apr 18;67(4):e0143822. doi: 10.1128/aac.01438-22. Epub 2023 Mar 28. PubMed 36975792 ↗
  • Tenero D, Derimanov G, Carlton A, Tonkyn J, Davies M, Cozens S, Gresham S, Gaudion A, Puri A, Muliaditan M, Rullas-Trincado J, Mendoza-Losana A, Skingsley A, Barros-Aguirre D. First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00240-19. doi: 10.1128/AAC.00240-19. Print 2019 Aug. PubMed 31182528 ↗
  • Li X, Hernandez V, Rock FL, Choi W, Mak YSL, Mohan M, Mao W, Zhou Y, Easom EE, Plattner JJ, Zou W, Perez-Herran E, Giordano I, Mendoza-Losana A, Alemparte C, Rullas J, Angulo-Barturen I, Crouch S, Ortega F, Barros D, Alley MRK. Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656). J Med Chem. 2017 Oct 12;60(19):8011-8026. doi: 10.1021/acs.jmedchem.7b00631. Epub 2017 Sep 27. PubMed 28953378 ↗
09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Jan 2024 (actual). Primary completion is estimated for Feb 2027, 37 months after the start.

Of 33 non-industry phase 2 interventional studies under Tuberculosis, Pulmonary, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 49. This study's planned 37 months is above that.

Counting every sponsor, half of 43 studies reached it within 30 months; a quarter within 21 and three quarters within 37.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 17, 2023
First posted
Nov 2, 2023
StartActual
Jan 9, 2024
Primary completionEst.
Feb 24, 2027
CompletionEst.
Aug 11, 2027
Last update
Oct 15, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Sponsor
Collaborators added: University of Milan·LMU Klinikum; collaborators removed: University of Milano·Ludwig-Maximilians - University of Munich
Oct 15, 2026
Show all 1 update
  1. Oct 15, 2026
    Sponsor Collaborators added: University of Milan·LMU Klinikum; collaborators removed: University of Milano·Ludwig-Maximilians - University of Munich
    + 2 other changes: verification date and description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06114628
Lead sponsor
University College, London
Collaborators
Radboud University Medical Center, London School of Hygiene and Tropical Medicine, University of Oxford, Research Center Borstel, Lygature, TASK Applied Science, Università Vita-Salute San Raffaele, Helmholtz Zentrum Munchen, KNCV Tuberculosis Foundation, Critical Path Institute, European Lung Foundation, Instituto de Saude Publica da Universidade do Porto, University of Liverpool, Institut de Recherche pour le Developpement, University of Hamburg-Eppendorf, University of California, San Francisco, TB Alliance, Find, University of Milan, University of St Andrews, Uppsala University, European Respiratory Society, Tuberculosis Network European Trialsgroup, Janssen, LP, Otsuka Pharmaceutical Development & Commercialization, Inc., German Center for Infection Research, LMU Klinikum, University of Cambridge, GlaxoSmithKline
Responsible party
Sponsor
First posted
Nov 2, 2023
Start date
Jan 9, 2024
Primary completion
Feb 24, 2027 (estimated)
Completion
Aug 11, 2027 (estimated)
Last update
Oct 15, 2026

Study contacts

Susie Slater
Contact
mrcctu.paradigm4tb@ucl.ac.uk
20 7670 4789 ext. +44
Karen Sanders
Contact
karen.sanders@ucl.ac.uk
2076704826 ext. +44

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: BTZ-043 · Bedaquiline · OPC-67683 · Pretomanid · Moxifloxacin · Linezolid · Pyrazinamide · Quabodepistat

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