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

NCT03896685 | Completed Phase 3 DMC

• 1 other identifier: MSF ERB-1761
• Study Type: interventional
• Target: 323
• Locations: 6 countries
• Sites: 10

Brief 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.

Conditions

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

Keywords

bedaquiline; delamanid; linezolid; clofazimine; tuberculosis; MDR-TB; XDR-TB

Outcome Measures

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.

  Week 73 after randomization

Secondary Outcomes (11)

• Week 104 Efficacy: Proportion of participants with favorable outcome at Week 104

  Week 104 after randomization

• Early Treatment Response (culture conversion)

  Week 8 after randomization

• Week 39 Efficacy: Proportion of participants with favorable outcome at Week 39

  Week 39 after randomization

• Week 73 Failure/Relapse

  Week 73 after randomization

• Week 104 Failure/Relapse

  Week 104 after randomization

Study Arms (2)

endTB-Q: BeDeCLi 24 or 39 weeks

EXPERIMENTAL

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

endTB-Q: Control arm

ACTIVE COMPARATOR

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 100 MG DRUG

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

Also known as: TMC207

endTB-Q: BeDeCLi 24 or 39 weeks

Delamanid 50 MG Oral Tablet DRUG

Delamanid: 100 mg BID

endTB-Q: BeDeCLi 24 or 39 weeks

Clofazimine 100 MG Oral Capsule DRUG

Clofazimine: 100 mg QD

endTB-Q: BeDeCLi 24 or 39 weeks

Linezolid 600Mg Tab DRUG

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

endTB-Q: BeDeCLi 24 or 39 weeks

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

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

endTB-Q: Control arm

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• b. 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.
• \. Has one or more of the following:
• 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.
• \. 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;

Sponsors & Collaborators

• Médecins Sans Frontières, France: lead
• Partners in Health: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Epicentre: collaborator
• Institute of Tropical Medicine, Belgium: collaborator
• Socios En Salud, Peru: collaborator
• Interactive Research and Development: collaborator
• University of San Francisco: collaborator

Study Sites (10)

Aundh Chest Hospital

Pune, India

Location

National Center for Tuberculosis Problems

Almaty, Kazakhstan

Location

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

Almaty, Kazakhstan

Location

Partners In Health Lesostho

Maseru, Lesotho

Location

The Indus Hospital

Karachi, Pakistan

Location

Institute of Chest Disease,

Kotri, Pakistan

Location

Centro de Investigación del Hospital Nacional Hipólito Unanue

Lima, 1390, Peru

Location

Centro de Investigación de Enfermedades Neumológicas del Hospital Nacional Sergio Bernales

Lima, Peru

Location

Hanoi Lung Hospital

Hanoi, Vietnam

Location

Pham Ngoc Thach Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (2)

• 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.

  PMID: 40683298 DERIVED

• 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.

  PMID: 38037119 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Tuberculosis; Tuberculosis, Pulmonary; Mycobacterium Infections; Bacterial Infections; Gram-Positive Bacterial Infections; Extensively Drug-Resistant Tuberculosis

Interventions

bedaquiline; OPC-67683; Tablets; Clofazimine; Linezolid

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Phenazines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Lorenzo Guglielmetti, MD

  Médecins Sans Frontières, France

  PRINCIPAL INVESTIGATOR

• Carole Mitnick, Sc.D

  Harvard Medical School (HMS and HSDM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 1, 2019
• Study Start: April 6, 2020
• Primary Completion: October 4, 2024
• Study Completion: December 31, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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)

Locations

LE (1); IN (1); VN (2); PA (2); KA (2); PE (2)