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Tuberculosis, Multidrug-ResistantPhase 3endTB-QNCT03896685

Evaluating Newly Approved Drugs in Combination Regimens for Multidrug-Resistant TB With Fluoroquinolone Resistance (endTB-Q)

A Phase 3 study testing Bedaquiline 100 MG, Delamanid 50 MG Oral Tablet and Clofazimine 100 MG Oral Capsule in people with Tuberculosis, Multidrug-Resistant and Tuberculosis, run by Médecins Sans Frontières, France at 10 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

endTB-Q Clinical Trial is a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of two new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB) with fluoroquinolone resistance. Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Bedaquiline 100 MG, Delamanid 50 MG Oral Tablet and Clofazimine 100 MG Oral Capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
323 participants
Where
10 sitesin 6 countries
Study dates
6 Apr 2020to 31 Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to rifampin (RIF) and not susceptible to fluoroquinolones, according to a validated rapid molecular test. Patients with RIF-resistant TB who are unable to tolerate fluoroquinolones (history of severe adverse events, allergies, hypersensitivity) are also eligible, regardless of resistance/susceptibility to fluoroquinolones;
  • Is ≥15 years of age;
  • Is willing to use contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilized must agree to use contraception unless their partner has had a vasectomy; men who have not had a vasectomy must agree to use condoms;
  • Provides informed consent for study participation; additionally a legal representative of patients considered minor per local laws should also provide consent;
  • Lives in a dwelling that can be located by study staff and expects to remain in the area for the duration of the study.

Who cannot join

  • 1. Has known allergies or hypersensitivity to any of the investigational drugs; 2. Is known to be pregnant or is unwilling or unable to stop breastfeeding an infant; 3. Is unable to comply with treatment or follow-up schedule; 4. Has any condition (social or medical) which, in the opinion of the site principal investigator, would make study participant unsafe; 5. a. Has had exposure (intake of the drug for 30 days or more) in the past five years to bedaquiline, delamanid, linezolid, or clofazimine, or has proven or likely resistance to bedaquiline, delamanid, linezolid, or clofazimine (e.g., household contact of a DR-TB index case who died or experienced treatment failure after treatment containing bedaquiline, delamanid, linezolid, or clofazimine or had resistance to one of the listed drugs); exposure to other anti-TB drugs is not a reason for exclusion.
  • Has received second-line drugs for 15 days or more prior to screening visit date in the current MDR/RR-TB treatment episode. Exceptions include:
  • patients whose treatment has failed according to the WHO definition and who are being considered for a new treatment regimen;
  • patients starting a new treatment regimen after having been "lost to follow-up" according to the WHO definition and,
  • patients in whom treatment failure is suspected (but not confirmed according to WHO definition), who are being considered for a new treatment regimen, and for whom the Clinical Advisory Committee (CAC) consultation establishes eligibility.
  • 6. Has one or more of the following:
Show all 28Show fewer
  • Hemoglobin ≤7.9 g/dL;
  • Uncorrectable electrolytes disorders:
  • Total Calcium <7.0 mg/dL (1.75 mmol/L);
  • Potassium <3.0 mEq/L (3.0 mmol/L) or ≥6.0 mEq/L (6.0 mmol/L);
  • Magnesium <0.9 mEq/L (0.45 mmol/L);
  • Serum creatinine >3 x ULN;
  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥3 x ULN;
  • Total bilirubin ≥3 x ULN; Unless otherwise specified, Grade 4 result as defined by the MSF Severity Scale on any of the screening laboratory tests.
  • 7. Has cardiac risk factors defined as:
  • An arithmetic average of the two ECGs with highest QTcF intervals of greater than or equal to 450 ms. Retesting to reassess eligibility will be allowed using an unscheduled visit during the screening phase;
  • Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome);
  • Electrocardiographic evidence of either:
  • Complete left bundle branch block or right bundle branch block; OR
  • Incomplete left bundle branch block or right bundle branch block and QRS complex duration greater than or equal to 120 msec on at least one ECG; • Having a pacemaker implant;
  • Congestive heart failure;
  • Evidence of second or third degree heart block;
  • Bradycardia as defined by sinus rate less than 50 bpm;
  • Personal or family history of Long QT Syndrome;
  • Personal history of arrhythmic cardiac disease, with the exception of sinus arrhythmia;
  • Personal history of syncope (i.e. cardiac syncope not including syncope due to vasovagal or epileptic causes).
  • 8. Concurrent participation in another trial of any medication used or being studied for TB treatment, as defined in cited documents.
  • 9. Is taking any medication that is contraindicated with the medicines in the trial regimen which cannot be stopped (with or without replacement) or requires a wash-out period longer than 2 weeks.

Trial locations and contacts

10 sites in 6 countries.

10 sites in 6 countries

Kazakhstan2 sites

  • National Center for Tuberculosis Problems

    Almaty

  • State Municipal Enterprise on the right of economic management "City Centre of Phthisiopulmonology" of Nur-sultan city's administration

    Almaty

Other trials in Kazakhstan

Pakistan2 sites

  • The Indus Hospital

    Karachi

  • Institute of Chest Disease,

    Kotri

Other trials in Pakistan

Peru2 sites

  • Centro de Investigación del Hospital Nacional Hipólito Unanue

    Lima, 1390

  • Centro de Investigación de Enfermedades Neumológicas del Hospital Nacional Sergio Bernales

    Lima

Other trials in Peru

Vietnam2 sites

  • Hanoi Lung Hospital

    Hanoi

  • Pham Ngoc Thach Hospital

    Ho Chi Minh City

Other trials in Vietnam

India1 site

  • Aundh Chest Hospital

    Pune

Other trials in India

Lesotho1 site

  • Partners In Health Lesostho

    Maseru

Other trials in Lesotho

About this study

endTB-Q Clinical Trial is a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of two new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB) with fluoroquinolone resistance.

Read the detailed description

This is a Phase III, randomized, controlled, open-label, multi-country trial evaluating the efficacy of new combination regimens for treatment of fluoroquinolone-resistant MDR-TB.

Regimens examined combine newly approved drugs bedaquiline and delamanid with existing drugs known to be active against Mycobacterium tuberculosis (linezolid and clofazimine). The study will enroll in parallel across 1 experimental and 1 standard-of-care control arms, in a 2:1 ratio. Randomization will be stratified by country and extent-of-TB-disease phenotype. In the experimental arm, treatment will be for 24 or 39 weeks; duration will be assigned according to extent-of-TB-disease phenotype and treatment response. In the control arm, treatment will be delivered according to WHO guidelines (and local practice); duration will be variable. Trial participation in both arms will last at least until Week 73, and up to Week 104.

Non-inferiority will be established for the experimental arm if the lower bound of the one-sided 97.5% confidence interval around the difference in favorable outcome between the control and experimental arms is greater than or equal to -12%.

Being tested
Bedaquiline 100 MG, Delamanid 50 MG Oral Tablet, Clofazimine 100 MG Oral Capsule, Linezolid 600Mg Tab, Control arm MDR-TB regimen, designed according to latest WHO guidelines
Keywords
bedaquiline, delamanid, linezolid, clofazimine, tuberculosis, MDR-TB, XDR-TB
Medical subject headings
Tuberculosis, Multidrug-Resistant, Tuberculosis, Tuberculosis, Pulmonary, Mycobacterium Infections, Bacterial Infections, Gram-Positive Bacterial Infections, Extensively Drug-Resistant Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bedaquiline 100 MGDrug

    Also called TMC207

    Bedaquiline: 400 mg QD x 2 weeks, followed by 200 mg 3x/week

  • Delamanid 50 MG Oral TabletDrug

    Delamanid: 100 mg BID

  • Clofazimine 100 MG Oral CapsuleDrug

    Clofazimine: 100 mg QD

  • Linezolid 600Mg TabDrug

    Linezolid: 600 mg QD up to Week 16, followed by 300 mg QD or 600 mg 3x/week according to a secondary randomization

  • Control arm MDR-TB regimen, designed according to latest WHO guidelinesDrug

    Control arm MDR-TB regimen, designed according to latest WHO guidelines (might include bedaquiline, delamanid, linezolid, clofazimine, or all of these drugs).

Study groups in NCT03896685
Study groupRoleWhat they receive
endTB-Q: BeDeCLi 24 or 39 weeksExperimentalendTB-Q regimen: bedaquiline-delamanid-linezolid-clofazimine (BeDeCLi). Subjects who are randomized to this arm will be assigned to duration of 24 or 39 weeks , according to the participant's extent-of-TB-disease phenotype. Participants may take as long as 32 weeks to complete all doses of a 24-week treatment regimen, and up to 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of the experimental regimens will be oral and weight based.
Receives: Drug: Bedaquiline 100 MG; Drug: Delamanid 50 MG Oral Tablet; Drug: Clofazimine 100 MG Oral Capsule; Drug: Linezolid 600Mg Tab
endTB-Q: Control armActive comparatorendTB-Q is the control regimen, designed according to latest World Health Organization guidelines.
Receives: Drug: Control arm MDR-TB regimen, designed according to latest WHO guidelines

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Week 73 Efficacy: Proportion of participants with favorable outcome at Week 73

    Proportion of participants with favorable outcome at Week 73. A participant's outcome will be classified as favorable at Week 73 if the outcome is not classified as unfavorable, and one of the following is true:

    1. The last two culture results are negative. These two cultures must be taken from sputum samples collected on separate visits, the latest between Week 65 and Week 73;
    2. The last culture result (from a sputum sample collected between Week 65 and Week 73) is negative; and either there is no other post-baseline culture result or the penultimate culture result is positive due to laboratory cross contamination; and bacteriological, radiological and clinical evolution is favorable;
    3. There is no culture result from a sputum sample collected between Week 65 and Week 73 or the result of that culture is positive due to laboratory cross contamination; and the most recent culture result is negative; and bacteriological, radiological and clinical evolution is favorable.

    Measured: Week 73 after randomization

Secondary outcomes (11)

  1. Week 104 Efficacy: Proportion of participants with favorable outcome at Week 104

    Proportion of participants with favorable outcome at Week 104. A participant's outcome will be classified as favorable at Week 104 if the outcome is not classified as unfavorable, and one of the following is true:

    1. The last two cultures are negative. These two cultures must be from sputum samples collected on separate visits, the latest between Week 97 and Week 104;
    2. The last culture result (from a sputum sample collected between Week 97 and Week 104) is negative; and either there is no other post-baseline culture result or the penultimate culture result is positive due to laboratory cross contamination; and bacteriological, radiological and clinical evolution is favorable;
    3. There is no culture result from a sputum sample collected between Week 97 and Week 104 or the result of that culture is positive due to laboratory cross contamination; and the most recent culture result is negative; and bacteriological, radiological and clinical evolution is favorable.

    Measured: Week 104 after randomization

  2. Early Treatment Response (culture conversion)

    1. Proportion of patients with culture conversion assessed in MGIT system (and LJ where possible): 2 consecutive negative cultures from specimens collected at 2 different visits; if there is a missing or contaminated culture between 2 negatives, the definition of conversion is still met;
    2. Time to culture conversion: assessed in MGIT system (and LJ where possible): time from treatment initiation to first of 2 consecutive negative cultures; if there is a missing or contaminated culture between 2 negatives, the definition of conversion is still met;
    3. Change in time to positivity (TTP) in MGIT over first 8 weeks.

    Measured: Week 8 after randomization

  3. Week 39 Efficacy: Proportion of participants with favorable outcome at Week 39

    Proportion of participants with favorable outcome at Week 39. A participant's outcome will be classified as favorable at Week 39 if all culture results from samples collected between Week 36 and Week 39 are negative and the outcome is not classified as unfavorable.

    A participant's outcome will be classified as unfavorable at Week 39 in case of:

    1. In the experimental arm, addition or replacement of one or more drugs;
    2. In the control arm, addition or replacement of two or more drugs;
    3. Death from any cause;
    4. At least one culture result (from a sample collected between Week 36 and Week 39) is positive;
    5. The patient is not assessable because the last available culture result is from a sample collected before Week 36;

    Measured: Week 39 after randomization

  4. Week 73 Failure/Relapse

    Proportion of participants with treatment failure/relapse. A participant's outcome will be classified as failure/relapse at Week 73 if:

    1. In an experimental arm, addition or replacement of one or more drugs;
    2. In the control arm, addition or replacement of two or more drugs;
    3. Initiation of a new MDR-TB regimen after the end of the allocated study regimen and before Week 73;
    4. At least one of the last two cultures, the latest between Week 65 and 73, is positive in the absence of cross contamination;
    5. The last culture result between Week 65 and 73 is negative; and: there is no other post-baseline culture result or the penultimate culture is positive due to cross contamination; and bacteriological, radiological or clinical evolution is unfavorable;
    6. There is no culture result between Week 65 and 73 or it is positive due to cross contamination; and: the most recent culture is negative; and bacteriological, radiological or clinical evolution is unfavorable.

    Measured: Week 73 after randomization

  5. Week 104 Failure/Relapse

    Proportion of participants with treatment failure/relapse. A participant's outcome will be classified as failure/relapse at Week 104 if:

    1. In an experimental arm, addition or replacement of one or more drugs;
    2. In the control arm, addition or replacement of two or more drugs;
    3. Initiation of a new MDR-TB treatment regimen after the end of the allocated study regimen and before Week 104;
    4. At least one of the last two cultures, the latest between Week 97 and 104, is positive in the absence of cross contamination;
    5. The last culture result between Week 97 and 104 is negative; and: there is no other post-baseline culture result or the penultimate culture is positive due to cross contamination; and bacteriological, radiological or clinical evolution is unfavorable;
    6. There is no culture result between Week 97 and 104 or it is positive due to cross contamination; and: the most recent culture is negative; and bacteriological, radiological or clinical evolution is unfavorable.

    Measured: Week 104 after randomization

  6. Week 73 Survival

    At 73 weeks, the proportion of patients who died of any cause

    Measured: Week 73 after randomization

  7. Week 104 Survival

    At 104 weeks, the proportion of patients who died of any cause

    Measured: Week 104 after randomization

  8. Week 73 AEs and SAEs

    The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 73 weeks

    Measured: Week 73 after randomization

  9. Week 104 AEs and SAEs

    The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 104 weeks

    Measured: Week 104 after randomization

  10. Week 73 AESIs

    The proportion of participants with adverse events of special interest (AESIs) by 73 weeks

    Measured: Week 73 after randomization

  11. Week 104 AESIs

    The proportion of participants with adverse events of special interest (AESIs) by 104 weeks

    Measured: Week 104 after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2019
  2. Study start6 Apr 2020
  3. Primary completion4 Oct 2024
  4. Study completion31 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
323 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03896685
Sponsor's protocol ID
MSF ERB-1761
Acronym
endTB-Q
Status last verified
Feb 2025
First submitted
28 Mar 2019
Last updated
10 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After deidentification process most part of variables recorded in the eCRF (no patients name or ID, no site or country location, no dates but intervals from randomization, no birth dates but age at randomization, no information on staff...).

Publications

  • Guglielmetti L, Khan U, Velasquez GE, Gouillou M, Ali MH, Amjad S, Kamal F, Abubakirov A, Ardizzoni E, Baudin E, Bektassov S, Berry C, Bonnet M, Chavan V, Coutisson S, Dakenova Z, de Jong BC, Dinh LV, Ferlazzo G, Kirakosyan O, Lachenal N, Lecca L, McIlleron H, Mikanda KK, Mucching-Toscano S, Mulders W, Mushtaque H, Nahid P, Nguyen DV, Nguyen NV, Oyewusi L, Motta I, Panda S, Patil S, Pham TH, Phan DT, Phan HTT, Phillips PPJ, Ruiz J, Rupasinghe P, Salahuddin N, Sanchez-Garavito E, Seung KJ, Asfaw MT, Vargas Vasquez D, Rich ML, Varaine F, Mitnick CD; endTB-Q Clinical Trial Team. Bedaquiline, delamanid, linezolid, and clofazimine for rifampicin-resistant and fluoroquinolone-resistant tuberculosis (endTB-Q): an open-label, multicentre, stratified, non-inferiority, randomised, controlled, phase 3 trial. Lancet Respir Med. 2025 Sep;13(9):809-820. doi: 10.1016/S2213-2600(25)00194-8. Epub 2025 Jul 16.

    PubMed 40683298

  • Patil SB, Tamirat M, Khazhidinov K, Ardizzoni E, Atger M, Austin A, Baudin E, Bekhit M, Bektasov S, Berikova E, Bonnet M, Caboclo R, Chaudhry M, Chavan V, Cloez S, Coit J, Coutisson S, Dakenova Z, De Jong BC, Delifer C, Demaisons S, Do JM, Dos Santos Tozzi D, Ducher V, Ferlazzo G, Gouillou M, Khan U, Kunda M, Lachenal N, LaHood AN, Lecca L, Mazmanian M, McIlleron H, Moreau M, Moschioni M, Nahid P, Osso E, Oyewusi L, Panda S, Paquet A, Thuong Huu P, Pichon L, Rich ML, Rupasinghe P, Salahuddin N, Sanchez Garavito E, Seung KJ, Velasquez GE, Vallet M, Varaine F, Yuya-Septoh FJ, Mitnick CD, Guglielmetti L. Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial. Trials. 2023 Nov 30;24(1):773. doi: 10.1186/s13063-023-07701-6.

    PubMed 38037119

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bedaquiline 100 MG, Delamanid 50 MG Oral Tablet and Clofazimine 100 MG Oral Capsule in people with Tuberculosis, Multidrug-Resistant and Tuberculosis, run by Médecins Sans Frontières, France at 10 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Kazakhstan, Pakistan, Peru, Vietnam, India and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Week 73 Efficacy: Proportion of participants with favorable outcome at Week 73 (time frame: Week 73 after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03896685, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.

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