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Tuberculosis, Multidrug-ResistantPhase 3endTBNCT02754765

Evaluating Newly Approved Drugs for Multidrug-resistant TB

A Phase 3 study testing Bedaquiline, Delamanid and Clofazimine in people with Tuberculosis, Multidrug-Resistant and Infection, Bacterial, run by Médecins Sans Frontières, France at 12 sites in 7 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 Clinical Trial a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of five new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB). Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Bedaquiline, Delamanid and Clofazimine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
754 participants
Where
12 sitesin 7 countries
Study dates
Dec 2016to Jun 2023
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

  • A patient will be eligible for randomization if s/he:
  • Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to rifampin (RIF) and susceptible to fluoroquinolones, diagnosed by validated rapid molecular test;
  • 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

  • A patient will not be eligible for randomization if s/he:
  • Has known allergies or hypersensitivity to any of the investigational drugs;
  • Is known to be pregnant or is unwilling or unable to stop breast-feeding an infant;
  • Is unable to comply with treatment or follow-up schedule;
  • Any condition (social or medical) which, in the opinion of the site principal investigator, would make study participant unsafe;
  • 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.
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  • 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: (1) patients whose treatment has failed according to the WHO definition151 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 definition149 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.
  • Has one or more of the following:
  • Hemoglobin ≤ 7.9 g/dL;
  • Uncorrectable electrolytes disorders:
  • Calcium < 7.0 mg/dL;
  • Potassium < 3.0 or ≥6.0 mEq/L;
  • Magnesium < 0.9 mEq/L;
  • Serum creatinine > 3 x ULN;
  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 3 x ULN;
  • Total bilirubin ≥ 1.5 x ULN if accompanied by AST or ALT > ULN or total bilirubin ≥ 2 x ULN when other liver function results are in the normal range;
  • Grade 4 result on any of the specified laboratory tests as defined by the MSF Severity Scale.
  • Has cardiac risk factors defined as:
  • A confirmed QTc interval of greater than or equal to 450 ms. Retesting to reassess eligibility will be allowed once 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 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).
  • Concurrent participation in another trial of any medication used or being studied for TB treatment, as defined in cited documents.
  • 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

12 sites in 7 countries.

12 sites in 7 countries

Kazakhstan3 sites

  • City Centre of Phthisiopulmonology

    Almaty, 020000

  • Center of Phthisiopulmonology of Almaty Health Department

    Almaty, 050030

  • National Center for Tuberculosis Problems

    Almaty

Other trials in Kazakhstan

Peru3 sites

  • Centro de Investigación del Hospital Nacional Hipólito Unanue

    Lima, 1390

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

    Lima

  • Hospital Nacional Dos de Mayo Parque Historia de la Medicina

    Lima

Other trials in Peru

Pakistan2 sites

  • The Indus Hospital

    Karachi

  • Institute of Chest Disease,

    Kotri

Other trials in Pakistan

Georgia1 site

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi, 0101

Other trials in Georgia

India1 site

  • Aundh Chest Hospital

    Pune

Other trials in India

Lesotho1 site

  • Partners In Health Lesostho

    Maseru

Other trials in Lesotho

South Africa1 site

  • Medecins Sans Frontieres Belgium

    Khayelitsha, 7784

Other trials in South Africa

About this study

Official title: Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB): A Clinical Trial

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

Read the detailed description

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

Regimens examined combine newly approved drugs bedaquiline and/or delamanid with existing drugs known to be active against Mycobacterium tuberculosis (linezolid, clofazimine, moxifloxacin or levofloxacin, and pyrazinamide). The study will enroll in parallel across 5 experimental and 1 standard-of-care control arms. Randomization will be outcome adapted using Bayesian interim analysis of efficacy endpoints. Experimental regimens will contain bedaquiline and/or delamanid and up to 4 companion drugs. Control-arm treatment may contain one of the following (bedaquiline or delamanid) and companion drugs, constructed and delivered according to local standard of care and consistent with WHO guidelines. Trial participation in all arms will last at least until Week 73, and up to Week 104. In the experimental arms, treatment will be for 39 weeks (participants in the experimental arms will be allowed up to 47 weeks to complete the 39-week treatment course) and post-treatment follow up for up to 65 additional weeks. In the control arm, treatment will be delivered according to local standard of care (in consistence with WHO guidance); duration may vary and will be approximately 86 weeks for the conventional regimen and 39-52 weeks for the standardized shorter regimen.

Non-inferiority will be established for any 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, Delamanid, Clofazimine, Levofloxacin, Moxifloxacin
Keywords
bedaquiline, delamanid, linezolid, clofazimine, tuberculosis, MDR-TB XDR-TB
Medical subject headings
Tuberculosis, Multidrug-Resistant, Bacterial Infections, Tuberculosis, Pulmonary, Tuberculosis

What participants receive

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

  • BedaquilineDrug

    Also called Sirturo

  • DelamanidDrug

    Also called Deltyba, OPC-67683

  • ClofazimineDrug

    Also called Lamprene

  • LevofloxacinDrug

  • MoxifloxacinDrug

  • LinezolidDrug

  • PyrazinamideDrug

  • Control arm MDR-TB regimen, consistent with WHO guidelinesDrug

    Control arm MDR-TB regimen, consistent WHO guidelines

Study groups in NCT02754765
Study groupRoleWhat they receive
endTB regimen 1 (BeLiMoZ)ExperimentalSubjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Receives: Drug: Bedaquiline; Drug: Moxifloxacin; Drug: Linezolid; Drug: Pyrazinamide
endTB regimen 2 (BeLiCLeZ)ExperimentalSubjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Receives: Drug: Bedaquiline; Drug: Clofazimine; Drug: Levofloxacin; Drug: Linezolid; Drug: Pyrazinamide
endTB regimen 3 (BeDeLiLeZ)ExperimentalSubjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Receives: Drug: Bedaquiline; Drug: Delamanid; Drug: Levofloxacin; Drug: Linezolid; Drug: Pyrazinamide
endTB regimen 4 (DeLiCLeZ)ExperimentalSubjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Receives: Drug: Delamanid; Drug: Clofazimine; Drug: Levofloxacin; Drug: Linezolid; Drug: Pyrazinamide
endTB regimen 5 (DeCMoZ)ExperimentalSubjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based.
Receives: Drug: Delamanid; Drug: Clofazimine; Drug: Moxifloxacin; Drug: Pyrazinamide
endTB regimen 6 (Control)Active comparatorendTB regimen 6 is the control regimen.
Receives: Drug: Control arm MDR-TB regimen, consistent with 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. 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:

    • The last two culture results are negative. These two cultures must be taken from sputum samples collected on separate visits, the latest between weeks 65 and 73;
    • The last culture result (from a sputum sample collected between weeks 65 and 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;
    • There is no culture result from a sputum sample collected between weeks 65 and 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 (9)

  1. Week 104 Efficacy

    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 weeks 97 and 104;
    2. The last culture result (from a sputum sample collected between weeks 97 and 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 weeks 97 and 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 8 weeks.

    Measured: Week 8 after randomization

  3. Week 39 Efficacy

    Proportion of participants with favorable outcome at week 39:

    • A participant's outcome will be classified as favorable at week 39 if the last culture result (from a sample collected between weeks 36 and 39) is 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 weeks 36 and 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 Survival

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

    Measured: Week 73 after randomization

  5. Week 104 Survival

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

    Measured: Week 104 after randomization

  6. Week 73 Safety

    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

  7. Week 104 Safety

    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

  8. Week 73 Safety: proportion of patients with AESIs

    The proportion of patients with AESIs by 73 weeks

    Measured: Week 73 after randomization

  9. Week 104 Safety: proportion of patients with AESIs

    The proportion of patients with 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 posted28 Apr 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionJun 2023
  4. Study completionJun 2023

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
754 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02754765
Sponsor's protocol ID
MSF ERB-1555
Acronym
endTB
Status last verified
Feb 2025
First submitted
25 Apr 2016
Last updated
10 Feb 2025
Results posted
No
Data monitoring committee
Yes
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, Abubakirov A, Baudin E, Berikova E, Berry C, Bonnet M, Cellamare M, Chavan V, Cox V, Dakenova Z, de Jong BC, Ferlazzo G, Karabayev A, Kirakosyan O, Kiria N, Kunda M, Lachenal N, Lecca L, McIlleron H, Motta I, Toscano SM, Mushtaque H, Nahid P, Oyewusi L, Panda S, Patil S, Phillips PPJ, Ruiz J, Salahuddin N, Garavito ES, Seung KJ, Ticona E, Trippa L, Vasquez DEV, Wasserman S, Rich ML, Varaine F, Mitnick CD; endTB Clinical Trial Team. Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis. N Engl J Med. 2025 Jan 30;392(5):468-482. doi: 10.1056/NEJMoa2400327.

    PubMed 39879593

  • Hewison C, Khan U, Bastard M, Lachenal N, Coutisson S, Osso E, Ahmed S, Khan P, Franke MF, Rich ML, Varaine F, Melikyan N, Seung KJ, Adenov M, Adnan S, Danielyan N, Islam S, Janmohamed A, Karakozian H, Kamene Kimenye M, Kirakosyan O, Kholikulov B, Krisnanda A, Kumsa A, Leblanc G, Lecca L, Nkuebe M, Mamsa S, Padayachee S, Thit P, Mitnick CD, Huerga H. Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort. Clin Infect Dis. 2022 Sep 29;75(6):1006-1013. doi: 10.1093/cid/ciac019.

    PubMed 35028659

  • Guglielmetti L, Ardizzoni E, Atger M, Baudin E, Berikova E, Bonnet M, Chang E, Cloez S, Coit JM, Cox V, de Jong BC, Delifer C, Do JM, Tozzi DDS, Ducher V, Ferlazzo G, Gouillou M, Khan A, Khan U, Lachenal N, LaHood AN, Lecca L, Mazmanian M, McIlleron H, Moschioni M, O'Brien K, Okunbor O, Oyewusi L, Panda S, Patil SB, Phillips PPJ, Pichon L, Rupasinghe P, Rich ML, Saluhuddin N, Seung KJ, Tamirat M, Trippa L, Cellamare M, Velasquez GE, Wasserman S, Zimetbaum PJ, Varaine F, Mitnick CD. Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial. Trials. 2021 Sep 25;22(1):651. doi: 10.1186/s13063-021-05491-3.

    PubMed 34563240

  • Seung KJ, Khan P, Franke MF, Ahmed S, Aiylchiev S, Alam M, Putri FA, Bastard M, Docteur W, Gottlieb G, Hewison C, Islam S, Khachatryan N, Kotrikadze T, Khan U, Kumsa A, Lecca L, Tassew YM, Melikyan N, Naing YY, Oyewusi L, Rich M, Wanjala S, Yedilbayev A, Huerga H, Mitnick CD. Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis. Clin Infect Dis. 2020 Jul 11;71(2):415-418. doi: 10.1093/cid/ciz1084.

    PubMed 31676905

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bedaquiline, Delamanid and Clofazimine in people with Tuberculosis, Multidrug-Resistant and Infection, Bacterial, run by Médecins Sans Frontières, France at 12 sites in 7 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 6 inclusion and 32 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 12 sites in Kazakhstan, Peru, Pakistan, Georgia, India and 2 more countries. 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 (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 NCT02754765, which also lists 4 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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