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

23 июня 2026 г. обновлено: 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.

Обзор исследования

Статус

Еще не набирают

Условия

Вмешательство/лечение

Подробное описание

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.

Тип исследования

Интервенционный

Регистрация (Оцененный)

294

Фаза

  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

  • Имя: Jae-Joon Yim, MD, PhD
  • Номер телефона: +82-2-2072-4029
  • Электронная почта: yimjj@snu.ac.kr

Учебное резервное копирование контактов

  • Имя: Young Ran Kim, RN, CRA
  • Номер телефона: +82-10-3588-5145
  • Электронная почта: oohri31@gmail.com

Места учебы

  • Южная Африка
    • North West
      • Klerksdorp, North West, Южная Африка, 2571
        • Perinatal HIV Research Unit, PHRU-Matlosana, Tshepong Hospital
        • Контакт:
        • Контакт:
        • Главный следователь:
          • Tumelo Moloantoa, MBChB
        • Главный следователь:
          • Ebrahim Variava, MD, FCP
    • Western Cape
      • Cape Town, Western Cape, Южная Африка, 7405
        • Desmond Tutu TB Centre, Brooklyn Chest Hospital Trial Unit
        • Контакт:
          • Vikesh Naidoo
          • Номер телефона: +27-65-811-9528
          • Электронная почта: dttcregulatory@sun.ac.za
        • Контакт:
        • Главный следователь:
          • Jennifer Hughes, MBBCh
        • Главный следователь:
          • Anneke Hesseling, MD, PhD

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

  • Ребенок
  • Взрослый
  • Пожилой взрослый

Принимает здоровых добровольцев

Нет

Описание

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.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: 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.
Другие имена:
  • Bedaquiline, delamanid, delpazolid, levofloxacin, and pyrazinamide
Активный компаратор: 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.
Лекарство: 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.
Другие имена:
  • South African standard of care treatment

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Favourable outcome at 12 months after treatment discontinuation
Временное ограничение: 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
Временное ограничение: 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

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Model-derived delpazolid AUC0-24
Временное ограничение: 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
Временное ограничение: 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.

Другие показатели результатов

Мера результата
Мера Описание
Временное ограничение
Time to sustained culture conversion
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Seoul National University Hospital

Соавторы

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

Следователи

  • Директор по исследованиям: Jeongha Mok, MD, PhD, Pusan National University Hospital
  • Главный следователь: Jennifer Hughes, MBBCh, Desmond Tutu TB Centre, Stellenbosch University
  • Учебный стул: Jae-Joon Yim, MD, PhD, Seoul National University Hospital

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

1 октября 2026 г.

Первичное завершение (Оцененный)

1 июня 2032 г.

Завершение исследования (Оцененный)

1 июня 2032 г.

Даты регистрации исследования

Первый отправленный

17 июня 2026 г.

Впервые представлено, что соответствует критериям контроля качества

23 июня 2026 г.

Первый опубликованный (Действительный)

30 июня 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

30 июня 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

23 июня 2026 г.

Последняя проверка

1 июня 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

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

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Описание плана 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.

Сроки обмена 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.

Критерии совместного доступа к 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.

Совместное использование IPD Поддерживающий тип информации

  • STUDY_PROTOCOL
  • САП
  • МКФ

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

продукт, произведенный в США и экспортированный из США.

Да

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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