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

23. června 2026 aktualizováno: Jae-Joon Yim, Seoul National University Hospital

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.

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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Odhadovaný)

294

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

  • Jméno: Jae-Joon Yim, MD, PhD
  • Telefonní číslo: +82-2-2072-4029
  • E-mail: yimjj@snu.ac.kr

Studijní záloha kontaktů

  • Jméno: Young Ran Kim, RN, CRA
  • Telefonní číslo: +82-10-3588-5145
  • E-mail: oohri31@gmail.com

Studijní místa

  • Jižní Afrika
    • North West
      • Klerksdorp, North West, Jižní Afrika, 2571
        • Perinatal HIV Research Unit, PHRU-Matlosana, Tshepong Hospital
        • Kontakt:
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Tumelo Moloantoa, MBChB
        • Vrchní vyšetřovatel:
          • Ebrahim Variava, MD, FCP
    • Western Cape
      • Cape Town, Western Cape, Jižní Afrika, 7405
        • Desmond Tutu TB Centre, Brooklyn Chest Hospital Trial Unit
        • Kontakt:
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Jennifer Hughes, MBBCh
        • Vrchní vyšetřovatel:
          • Anneke Hesseling, MD, PhD

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dítě
  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Male or female participants aged 15 years or older.

  4. 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.
  5. Not yet started rifampicin-resistant tuberculosis treatment, or initiated rifampicin-resistant tuberculosis treatment in routine care within 10 days prior to enrolment.
  6. Body weight of at least 30 kg.
  7. Documented HIV status and/or willing to undergo HIV testing.
  8. 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.
  9. Pregnant women in any trimester and breastfeeding women are eligible for inclusion.

Exclusion Criteria:

  1. 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.
  2. Ongoing treatment for rifampicin-resistant tuberculosis for more than 10 days in the current tuberculosis episode.
  3. Isolated extrapulmonary tuberculosis without pulmonary involvement.
  4. Extrapulmonary tuberculosis, with or without concurrent pulmonary tuberculosis, involving the central nervous system, osteoarticular sites, pericardium, or disseminated/miliary disease.

  5. 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.

  6. 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.
  7. 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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Investigational arm
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.
Lék: MDR-END Plus regimen
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.
Ostatní jména:
  • Bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide
Aktivní komparátor: Control arm
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.
Lék: Standard-of-care (SoC) 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.
Ostatní jména:
  • South African standard of care treatment

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Favourable outcome at 12 months after treatment discontinuation
Časové okno: 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
Časové okno: During treatment and up to 90 days after treatment discontinuation
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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Model-derived delpazolid AUC0-24
Časové okno: 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 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.
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
Časové okno: 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 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.
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.

Další výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Time to sustained culture conversion
Časové okno: From randomisation to the date of first documented sustained sputum culture conversion, assessed during the intended treatment period up to 18 months after randomisation.
Time from randomisation to sustained sputum culture conversion among participants with a positive baseline sputum culture, assessed using liquid media. Sustained sputum culture conversion is defined as two consecutive negative sputum cultures collected at least 7 days apart, with the date of conversion defined as the date of collection of the first negative culture.
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
Časové okno: 2 months after randomisation
Proportion of participants with a positive baseline sputum culture who achieve culture conversion at 2 months after randomisation, assessed using liquid media.
2 months after randomisation
Four-month culture conversion rate
Časové okno: 4 months after randomisation
Proportion of participants with a positive baseline sputum culture who achieve culture conversion at 4 months after randomisation, assessed using liquid media.
4 months after randomisation
Treatment success at end of treatment
Časové okno: At the end of the intended treatment period, assessed up to 20 months after randomisation.
Proportion of participants with treatment success, defined as cured or treatment completed, at the end of the intended treatment period.
At the end of the intended treatment period, assessed up to 20 months after randomisation.
Relapse after treatment success
Časové okno: Within 12 months after treatment discontinuation
Proportion of participants who achieve treatment success and subsequently experience TB or rifampicin-resistant TB relapse within 12 months after treatment discontinuation, as well as time to relapse.
Within 12 months after treatment discontinuation
All-cause mortality
Časové okno: From randomisation to 12 months after treatment discontinuation
All-cause mortality rate and time to death from randomisation to the end of the 12-month follow-up period after treatment discontinuation.
From randomisation to 12 months after treatment discontinuation
Other safety endpoints
Časové okno: During treatment and up to 90 days after treatment discontinuation
Incidence of specific adverse events occurring during treatment and up to 90 days after treatment discontinuation, including Grade 3 or higher adverse drug reactions, serious adverse drug reactions, and adverse events of special interest. Adverse events of special interest include QTcF >500 ms, increase from baseline in QTcF >60 ms, Grade 3 or higher hepatotoxicity, and oxazolidinone-related adverse drug reactions.
During treatment and up to 90 days after treatment discontinuation

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Seoul National University Hospital

Spolupracovníci

Korea University
Seoul National University
Perinatal HIV Research Unit of the University of the Witswatersrand
Desmond Tutu TB Centre
National Institute of Health, Korea

Vyšetřovatelé

  • Ředitel studie: Jeongha Mok, MD, PhD, Pusan National University Hospital
  • Vrchní vyšetřovatel: Jennifer Hughes, MBBCh, Desmond Tutu TB Centre, Stellenbosch University
  • Studijní židle: Jae-Joon Yim, MD, PhD, Seoul National University Hospital

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. října 2026

Primární dokončení (Odhadovaný)

1. června 2032

Dokončení studie (Odhadovaný)

1. června 2032

Termíny zápisu do studia

První předloženo

17. června 2026

První předloženo, které splnilo kritéria kontroly kvality

23. června 2026

První zveřejněno (Aktuální)

30. června 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

30. června 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

23. června 2026

Naposledy ověřeno

1. června 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • MDR-END Plus
  • 15075 (Identifikátor registru: South African National Clinical Trials Register (SANCTR))

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

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.

Časový rámec sdílení IPD

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.

Kritéria přístupu pro sdílení IPD

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.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY
  • MÍZA
  • ICF

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

produkt vyrobený a vyvážený z USA

Ano

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