Rifampicin-Resistant TuberculosisPhase 3MDR-ENDPlusNCT07675954
A 6-Month MDR-END Plus Regimen for Rifampicin-Resistant Tuberculosis
A Phase 3 study testing MDR-END Plus regimen and Standard-of-care (SoC) treatment in people with Rifampicin-Resistant Tuberculosis, run by Seoul National University Hospital at 2 sites in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Rifampicin-Resistant Tuberculosis
- What is being tested?
- MDR-END Plus regimen and Standard-of-care (SoC) treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 294 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 1 Oct 2026to Jun 2032
- Phase
- Phase 3
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
- 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
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- 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.
- Pregnant women in any trimester and breastfeeding women are eligible for inclusion.
Who cannot join
- 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.
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- 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:
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
South Africa2 sites
Desmond Tutu TB Centre, Brooklyn Chest Hospital Trial Unit
Cape Town, Western Cape, 7405
Vikesh Naidoo, +27-65-811-9528, dttcregulatory@sun.ac.za
Jennifer Hughes, MBBCh, jhughes@sun.ac.za
Perinatal HIV Research Unit, PHRU-Matlosana, Tshepong Hospital
Klerksdorp, North West, 2571
Priya Bhana, +27-11-989-9819, phruregulatory@phru.co.za
Tumelo Moloantoa, MBChB, moloantoat@phru.co.za
About this study
Official title: A Phase 3, Open-Label, Randomised Controlled Trial to Evaluate a 6-Month "MDR-END Plus" Regimen (Bedaquiline, Delamanid, Delpazolid, Levofloxacin and Pyrazinamide) Versus the South African Standard of Care Treatment for Rifampicin-Resistant Tuberculosis
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.
Read more
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.
Read the detailed description
This is a phase 3, multi-site, open-label, randomized controlled trial conducted in South Africa. The study will enroll adults and adolescents aged 15 years or older who require treatment for pulmonary rifampicin-resistant tuberculosis.
Participants will be randomized in a 1:1 ratio to either the investigational arm or the control arm. Randomization will be stratified by study site and HIV status. The study is open-label because participants and investigators will know which treatment is assigned.
Participants in the investigational arm will receive the MDR-END Plus regimen, consisting of bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide. Regimen adaptations may be made according to the drug susceptibility profile of the participant's Mycobacterium tuberculosis strain and drug suitability. Treatment may be extended according to protocol-defined criteria.
Participants in the control arm will receive South African standard of care (SoC) treatment for rifampicin-resistant tuberculosis according to national guidance and site practice.
Participants will attend study visits during treatment and after treatment discontinuation. Study assessments will include clinical evaluations, safety laboratory tests, electrocardiograms, microbiological assessments, and protocol-specified safety and tolerability assessments. Participants will be followed for 12 months after treatment discontinuation.
The primary efficacy analysis will assess whether the MDR-END Plus regimen is non-inferior to SoC regimens for favorable treatment outcome at 12 months after treatment discontinuation. The co-primary safety and tolerability analysis will assess whether the MDR-END Plus regimen is superior to SoC regimens during treatment and up to 90 days after treatment discontinuation, contingent upon demonstration of efficacy non-inferiority.
- Conditions
- Rifampicin-Resistant Tuberculosis
- Being tested
- MDR-END Plus regimen, Standard-of-care (SoC) treatment
- Keywords
- Rifampicin-resistant tuberculosis, Multidrug-resistant tuberculosis, MDR-TB, RR-TB, Bedaquiline, Delamanid, Delpazolid, Levofloxacin, Pyrazinamide, MDR-END Plus, Short treatment regimen, South Africa
- Medical subject headings
- Tuberculosis, Multidrug-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MDR-END Plus regimenDrug
Also called Bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide
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.
Standard-of-care (SoC) treatmentDrug
Also called South African standard of care treatment
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Standard-of-care (SoC) treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: During treatment and up to 90 days after treatment discontinuation
Secondary outcomes (2)
Model-derived delpazolid AUC0-24
Model-derived delpazolid area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) will be estimated from the final population pharmacokinetic model in participants receiving the MDR-END Plus regimen. This exposure metric will be used to support dose evaluation across predefined weight groups, including assessment of the effect of HIV status.
Measured: 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
Model-derived delpazolid maximum plasma concentration (Cmax) will be estimated from the final population pharmacokinetic model in participants receiving the MDR-END Plus regimen. This exposure metric will be used to support dose evaluation across predefined weight groups, including assessment of the effect of HIV status.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2026
- Study start1 Oct 2026 (estimated)
- Primary completionJun 2032 (estimated)
- Study completionJun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rifampicin-Resistant TuberculosisStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 294 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Seoul National University, Korea University, National Institute of Health, Korea, Desmond Tutu TB Centre, Perinatal HIV Research Unit of the University of the Witswatersrand
- Responsible party
- Principal investigator, Jae-Joon Yim, Seoul National University Hospital
- Investigators
- Jeongha Mok, MD, PhD, Study director, Pusan National University HospitalJennifer Hughes, MBBCh, Principal investigator, Desmond Tutu TB Centre, Stellenbosch UniversityJae-Joon Yim, MD, PhD, Study chair, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07675954
- Sponsor's protocol ID
- MDR-END Plus
- Other IDs
- 15075
- Acronym
- MDR-ENDPlus
- Status last verified
- Jun 2026
- First submitted
- 17 Jun 2026
- Last updated
- 30 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in this study will be made available. This includes participant-level data required to reproduce the primary and secondary outcomes, as well as associated data dictionaries. All data will be anonymized in accordance with applicable data protection regulations, including the Protection of Personal Information Act (POPIA) of South Africa.