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.
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.
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 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.
Parallel
MDR-END Plus regimen
DrugThe 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) treatment
DrugParticipants 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.
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.
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.
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.
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.
Time to sustained culture conversion
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.
Two-month culture conversion rate
Proportion of participants with a positive baseline sputum culture who achieve culture conversion at 2 months after randomisation, assessed using liquid media.
Four-month culture conversion rate
Proportion of participants with a positive baseline sputum culture who achieve culture conversion at 4 months after randomisation, assessed using liquid media.
Treatment success at end of treatment
Proportion of participants with treatment success, defined as cured or treatment completed, at the end of the intended treatment period.
Click on the lead sponsor to view all of their trials.
Seoul National University Hospital
Lead sponsor
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
This trial is not recruiting at the moment. You can still explore other options:
