ClinicalTrials.gg
CompletedNCT03896685endTB-QUpdated Feb 10, 2025

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

A Phase 3 interventional study of Bedaquiline 100 MG and Delamanid 50 MG Oral Tablet in Tuberculosis, Multidrug-Resistant, Tuberculosis and Pulmonary Tuberculoses, sponsored by Médecins Sans Frontières, France. Completed at 10 sites in 6 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2025-02-10.

Sponsored by Médecins Sans Frontières, France · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
323
Allocation
Randomized
Ages
15 Years and older
Sex
All
01

Study 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 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%.

02

Conditions studied

  • Tuberculosis, Multidrug-Resistant
  • Tuberculosis
  • Pulmonary Tuberculoses
  • Mycobacterial Infections
  • Bacterial Infections
  • Gram-Positive Bacterial Infections

Keywords

  • bedaquiline
  • delamanid
  • linezolid
  • clofazimine
  • tuberculosis
  • MDR-TB
  • XDR-TB
03

In context

Tuberculosis, Multidrug-Resistant

132 studies on the registry are indexed under Tuberculosis, Multidrug-Resistant; 25 are open to participants now.

This study's enrollment of 323 is above the median of 194 across 88 interventional studies indexed under Tuberculosis, Multidrug-Resistant.

Browse Tuberculosis, Multidrug-Resistant studies →

Lead sponsor

Médecins Sans Frontières, France is the lead sponsor of 2 studies on the registry; none are open to participants now.

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

04

Who can participate

Ages eligible
15 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. 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, ) are also eligible, regardless of resistance/susceptibility to fluoroquinolones;
  2. Is ≥15 years of age;
  3. Is willing to use : 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;
  4. Provides for study participation; additionally a legal representative of patients considered minor per local laws should also provide consent;
  5. Lives in a dwelling that can be located by study staff and expects to remain in the area for the duration of the study.

Exclusion criteria

Exclusion Criteria:

  1. Has known allergies or to any of the 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.

b. Has received drugs for 15 days or more prior to screening visit date in the current MDR/RR-TB treatment episode. Exceptions include:

  1. patients whose treatment has failed according to the WHO definition and who are being considered for a new treatment regimen;
  2. patients starting a new treatment regimen after having been "lost to follow-up" according to the WHO definition and,
  3. 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.
  1. Has one or more of the following:
  • ≤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 ;
    • (AST) or Alanine Aminotransferase (ALT) ≥3 x ULN;
    • Total ≥3 x ULN; Unless otherwise specified, Grade 4 result as defined by the MSF Severity Scale on any of the screening laboratory tests.

      1. Has cardiac risk factors defined as:
    • An arithmetic average of the two ECGs with highest 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 ; • 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).

      1. Concurrent participation in another trial of any medication used or being studied for TB treatment, as defined in cited documents.
      1. Is taking any medication that is with the medicines in the trial regimen which cannot be stopped (with or without replacement) or requires a longer than 2 weeks.
Terms in these criteria, in plain language(13)

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.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

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.

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.

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.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

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).

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.

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.

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.

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.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
323 participants (actual)

Study arms

  • Experimental
    endTB-Q: BeDeCLi 24 or 39 weeks

    endTB-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.

    Drug: Bedaquiline 100 MG · Drug: Delamanid 50 MG Oral Tablet · Drug: Clofazimine 100 MG Oral Capsule · Drug: Linezolid 600Mg Tab

  • Active comparator
    endTB-Q: Control arm

    endTB-Q is the control regimen, designed according to latest World Health Organization guidelines.

    Drug: Control arm MDR-TB regimen, designed according to latest WHO guidelines

Interventions

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

    Also known as: TMC207

  • Delamanid: 100 mg BID

  • Clofazimine: 100 mg QD

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

  • DrugControl arm MDR-TB regimen, designed according to latest WHO guidelines

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

06

What researchers measure

Primary outcomes

  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.

    Time frame: Week 73 after randomization

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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;

    Time frame: 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.

    Time frame: 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.

    Time frame: Week 104 after randomization

  6. Week 73 Survival

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

    Time frame: Week 73 after randomization

  7. Week 104 Survival

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

    Time frame: 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

    Time frame: 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

    Time frame: Week 104 after randomization

  10. Week 73 AESIs

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

    Time frame: Week 73 after randomization

  11. Week 104 AESIs

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

    Time frame: Week 104 after randomization

07

Study locations

10 sites
  • Aundh Chest Hospital
    Pune, India
  • National Center for Tuberculosis Problems
    Almaty, Kazakhstan
  • State Municipal Enterprise on the right of economic management "City Centre of Phthisiopulmonology" of Nur-sultan city's administration
    Almaty, Kazakhstan
  • Partners In Health Lesostho
    Maseru, Lesotho
  • The Indus Hospital
    Karachi, Pakistan
  • Institute of Chest Disease,
    Kotri, Pakistan
  • Centro de Investigación del Hospital Nacional Hipólito Unanue
    Lima, 1390, Peru
  • Centro de Investigación de Enfermedades Neumológicas del Hospital Nacional Sergio Bernales
    Lima, Peru
  • Hanoi Lung Hospital
    Hanoi, Vietnam
  • Pham Ngoc Thach Hospital
    Ho Chi Minh City, Vietnam
08

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: 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...).

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: From 2025 end and will last 4 years renewable.

Access criteria: proposal has scientific value / the scientific question addresses a knowledge gap and avoids duplication without added value and unnecessary competition, and benefits the wider public health community the data requested must be capable of answering the research question, and each variable requested must be required for the successful completion of the research the methodology proposed to answer the research question must be sound conform to the Data Access Guidelines, Ethics Framework, and Conflict of Interest Policy (see on website https://endtb.org/data-sharing-initiative)

Data sharing details ↗ · endtb.org

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 10, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03896685
Lead sponsor
Médecins Sans Frontières, France
Collaborators
Partners in Health, Harvard Medical School (HMS and HSDM), Epicentre, Institute of Tropical Medicine, Belgium, Socios En Salud, Peru, Interactive Research and Development, University of San Francisco
Responsible party
Sponsor
First posted
Apr 1, 2019
Start date
Apr 6, 2020
Primary completion
Oct 4, 2024
Completion
Dec 31, 2024
Last update
Feb 10, 2025

Study contacts

Lorenzo Guglielmetti, MD
principal investigator · Médecins Sans Frontières, France
Carole Mitnick, Sc.D
principal investigator · Harvard Medical School (HMS and HSDM)

Oversight

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

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This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Bedaquiline · OPC-67683 · Clofazimine · Linezolid

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