A 6-Month MDR-END Plus Regimen for Rifampicin-Resistant Tuberculosis

NCT07675954 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: MDR-END Plus15075
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase 3, open-label, randomized clinical trial in adults and adolescents aged 15 years or older who need treatment for rifampicin-resistant tuberculosis in South Africa. The goal of this clinical trial is to learn whether a 6-month MDR-END Plus regimen works as well as current standard of care (SoC) treatment for rifampicin-resistant tuberculosis. The trial will also learn whether the MDR-END Plus regimen is safer and easier to tolerate than SoC regimens. The main questions this trial aims to answer are:

• Does the MDR-END Plus regimen lead to a favorable treatment outcome 12 months after treatment is stopped, compared with SoC regimens?
• Do participants receiving the MDR-END Plus regimen have fewer important safety or tolerability problems during treatment and up to 90 days after treatment is stopped, compared with SoC regimens? Researchers will compare the MDR-END Plus regimen with South African standard of care (SoC) treatment for rifampicin-resistant tuberculosis. Participants will:
• Be randomly assigned to receive either the MDR-END Plus regimen or SoC treatment.
• Take tuberculosis medicines for about 6 months, although treatment may be extended in some cases.
• Attend study visits during treatment and after treatment is stopped.
• Have clinical assessments, blood tests, heart tracing tests, vision and nerve assessments, and tuberculosis tests.
• Be followed for 12 months after treatment is stopped.

Conditions

Rifampicin-Resistant Tuberculosis

Keywords

Rifampicin-resistant tuberculosis; Multidrug-resistant tuberculosis; MDR-TB; RR-TB; Bedaquiline; Delamanid; Delpazolid; Levofloxacin; Pyrazinamide; MDR-END Plus; Short treatment regimen; South Africa

Outcome Measures

Primary Outcomes (2)

• Favourable outcome at 12 months after treatment discontinuation

  Proportion of evaluable participants with a favourable outcome at 12 months after treatment discontinuation in the investigational arm compared with the control arm. The primary efficacy analysis will assess whether the MDR-END Plus regimen is non-inferior to SoC regimens.

  12 months after treatment discontinuation

• Composite safety and tolerability endpoint

  Proportion of evaluable participants meeting the predefined composite safety and tolerability endpoint during treatment and up to 90 days after treatment discontinuation in the investigational arm compared with the control arm. The co-primary safety and tolerability analysis will assess whether the MDR-END Plus regimen is superior to SoC regimens, contingent upon demonstration of efficacy non-inferiority. The composite endpoint includes protocol-defined adverse events, serious adverse events, adverse events of special interest, and adverse events leading to permanent discontinuation of any study drug.

  During treatment and up to 90 days after treatment discontinuation

Secondary Outcomes (2)

• Model-derived delpazolid AUC0-24

  Sparse PK sampling at Weeks 2, 8, and 26 after randomisation; intensive PK sampling at Week 2, pre-dose and 1, 2, 4, 8, and 24 hours post-dose.

• Model-derived delpazolid Cmax

  Sparse PK sampling at Weeks 2, 8, and 26 after randomisation; intensive PK sampling at Week 2, pre-dose and 1, 2, 4, 8, and 24 hours post-dose.

Other Outcomes (7)

• Time to sustained culture conversion

  From randomisation to the date of first documented sustained sputum culture conversion, assessed during the intended treatment period up to 18 months after randomisation.

• Two-month culture conversion rate

  2 months after randomisation

• Four-month culture conversion rate

  4 months after randomisation

Study Arms (2)

Investigational arm

EXPERIMENTAL

Participants assigned to the investigational arm will receive the 6-month MDR-END Plus regimen, consisting of bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide, with protocol-defined modifications based on drug susceptibility and drug suitability. Treatment may be extended up to 9 months according to protocol-defined criteria.

Drug: MDR-END Plus regimen

Control arm

ACTIVE COMPARATOR

Participants assigned to the control arm will receive standard of care (SoC) treatment for rifampicin-resistant tuberculosis according to South African national guidance and site practice.

Drug: Standard-of-care (SoC) treatment

Interventions

MDR-END Plus regimen DRUG

The investigational MDR-END Plus regimen consists of oral anti-tuberculosis drugs including bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide. Dosing and duration will follow the study protocol, with modifications based on body weight, drug susceptibility, drug suitability, and protocol-defined treatment extension criteria.

Also known as: Bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide

Investigational arm

Standard-of-care (SoC) treatment DRUG

Participants in the control arm will receive South African standard-of-care treatment for rifampicin-resistant tuberculosis according to national treatment guidance and site practice. The regimen may vary according to drug susceptibility results, drug suitability, and clinical judgement.

Also known as: South African standard of care treatment

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:

• Willing and able to voluntarily provide written informed consent to participate in the study prior to initiation of any study-related procedures. For participants under the age of 18 years, signed consent may be obtained from the child's biological parent, legal guardian, or primary caregiver in the presence of the child. Minor participants must also be willing to provide written assent for study participation.
• To the best of their knowledge and abilities at screening, participants must be willing and able to adhere to the complete follow-up schedule and all study procedures.
• Male or female participants aged 15 years or older.
• Participant requires treatment for pulmonary rifampicin-resistant tuberculosis based on one or more of the following:
• Documented molecular drug susceptibility testing, such as TB nucleic acid amplification test, line probe assay, targeted next-generation sequencing, or culture-based phenotypic drug susceptibility testing on a sample obtained from the participant within 8 weeks prior to screening, even if rifampicin resistance is not re-confirmed on a sample obtained at screening; or
• Documented or self-reported clinical symptoms or signs of pulmonary tuberculosis disease, with or without radiological changes consistent with pulmonary tuberculosis, and evidence of close contact with someone with confirmed rifampicin-resistant tuberculosis which, in the opinion of the site investigator, indicates significant exposure and a clinical decision has been made to treat the participant for rifampicin-resistant tuberculosis in routine care; or
• Documented peripheral tuberculosis lymphadenitis or tuberculosis pleurisy with confirmed rifampicin-resistant Mycobacterium tuberculosis on lymph node biopsy or pleural fluid aspiration, along with documented symptoms or signs suggestive of pulmonary tuberculosis without culture confirmation.
• Not yet started rifampicin-resistant tuberculosis treatment, or initiated rifampicin-resistant tuberculosis treatment in routine care within 10 days prior to enrolment.
• Body weight of at least 30 kg.
• Documented HIV status and/or willing to undergo HIV testing.
• Participants living with HIV must be on antiretroviral therapy, or due to start antiretroviral therapy within 2 months of enrolment, regardless of CD4 count, provided they are clinically stable in the opinion of the site investigator.

You may not qualify if:

• Two or more of the following four drug groups cannot be used: bedaquiline or clofazimine; delamanid or pretomanid; linezolid or delpazolid; levofloxacin or moxifloxacin, due to any of the following:
• Documented Mycobacterium tuberculosis resistance in the current or prior treatment episode;
• Prior exposure of 1 month or longer, unless protocol-defined exceptions are met;
• Absolute contraindications to the relevant study drugs;
• Use of prohibited concomitant medications within 14 days prior to enrolment.
• Ongoing treatment for rifampicin-resistant tuberculosis for more than 10 days in the current tuberculosis episode.
• Isolated extrapulmonary tuberculosis without pulmonary involvement.
• Extrapulmonary tuberculosis, with or without concurrent pulmonary tuberculosis, involving the central nervous system, osteoarticular sites, pericardium, or disseminated/miliary disease.
• Any of the following laboratory or ECG abnormalities:
• A. Alanine transaminase or aspartate transaminase \>120 U/L; B. Total bilirubin \>2.4 mg/dL; C. Estimated glomerular filtration rate by the CKD-EPI equation \<30 mL/min/1.73 m²; D. Serum potassium \<3.2 mmol/L; E. QTcF \>480 msec.
• Atrioventricular block, second or third degree; current or previous history of clinically significant ventricular arrhythmias or long QT syndrome; or family history of long QT syndrome or sudden cardiac death.
• Any condition or circumstance which, in the opinion of the investigator, based on information available at the time of screening, raises concerns regarding the participant's safety or ability to participate in the trial or the integrity of the study data.

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Seoul National University: collaborator
• Korea University: collaborator
• National Institute of Health, Korea: collaborator
• Desmond Tutu TB Centre: collaborator
• Perinatal HIV Research Unit of the University of the Witswatersrand: collaborator

Study Sites (2)

Perinatal HIV Research Unit, PHRU-Matlosana, Tshepong Hospital

Klerksdorp, North West, 2571, South Africa

Location

Desmond Tutu TB Centre, Brooklyn Chest Hospital Trial Unit

Cape Town, Western Cape, 7405, South Africa

Location

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

Clinical Protocols; bedaquiline; OPC-67683; delpazolid; Levofloxacin; Pyrazinamide; Standard of Care; Therapeutics

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Quality Indicators, Health Care; Health Services Administration

Study Officials

• Jeongha Mok, MD, PhD

  Pusan National University Hospital

  STUDY DIRECTOR

• Jennifer Hughes, MBBCh

  Desmond Tutu TB Centre, Stellenbosch University

  PRINCIPAL INVESTIGATOR

• Jae-Joon Yim, MD, PhD

  Seoul National University Hospital

  STUDY CHAIR

Central Study Contacts

Jae-Joon Yim, MD, PhD

CONTACT

+82-2-2072-4029; yimjj@snu.ac.kr

Young Ran Kim, RN, CRA

CONTACT

+82-10-3588-5145; oohri31@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label trial. Participants, investigators, and care providers will not be masked to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Participants will be randomized to one of two parallel treatment arms: the investigational arm receiving the MDR-END Plus regimen or the control arm receiving standard of care (SoC) treatment for rifampicin-resistant tuberculosis.

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: June 30, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 1, 2032
• Study Completion (Estimated): June 1, 2032
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available beginning 12 months following publication of the primary study results or completion of the study, whichever occurs first, and will remain available.
• Access Criteria: Requests must include a methodologically sound research proposal and will be subject to review and approval by the sponsor and local investigators. Data may be shared under a data access agreement, ensuring compliance with ethical standards, participant confidentiality, and applicable regulatory requirements.

Locations

ZA (2)