Clinical Trial: Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants With Pulmonary TB, XDR-TB, Pre- XDR-TB or Non-responsive/Intolerant MDR-TB (ZeNiX)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 3 Partially-blinded, Randomized Trial Assessing the Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants With Pulmonary Inf

Brief Summary: To evaluate the efficacy, safety and tolerability of various doses and durations of linezolid plus bedaquiline and pretomanid after 26 weeks of treatment in participants with either pulmonary XDR-TB, pre-XDR-TB, or treatment intolerant or non-responsive MDR-TB.

Detailed Summary:

A phase 3, multi-center, partially-blinded, randomized clinical trial in four parallel treatment groups. Bedaquiline and pretomanid treatment will not be blinded. Linezolid treatment dose and duration will be double-blinded.

Participants will have a screening period of up to 9 days and will be randomized to receive one of the 4 active treatment arms. Participants will be randomized to one of the four regimens in a 1:1:1:1 ratio, using an interactive web response system (IWRS) which will utilize a dynamic randomization system using minimization with a random element to allocate participants evenly across the arms by HIV status and type of TB.

Each participant will receive 26 weeks of treatment. If participant's week 16 sample remains culture positive, Investigator may consider extending current treatment to 39 weeks, in consultation with the Sponsor Medical Monitor

Participants will be followed for 78 weeks after end of treatment.


Sponsor: Global Alliance for TB Drug Development

Current Primary Outcome: Incidence of bacteriologic failure or relapse or clinical failure through follow up until 26 weeks after the end of treatment [ Time Frame: 26 weeks ]

Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of bacteriologic failure or relapse or clinical failure through follow up until 78 weeks after the end of treatment. [ Time Frame: 78 weeks ]
    Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart.
  • Time to sputum culture conversion to negative status through the treatment period [ Time Frame: 26 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 4 [ Time Frame: 4 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 6 [ Time Frame: 6 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 8 [ Time Frame: 8 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 12 [ Time Frame: 12 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 16 [ Time Frame: 16 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Proportion of participants with sputum culture conversion to negative status at week 26 [ Time Frame: 26 weeks ]
    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures
  • Change from baseline TB symptoms [ Time Frame: 26 weeks ]
    Severity of symptoms compared to start of treatment
  • Change from baseline in Patient Reported Health Status [ Time Frame: 26 weeks ]
    Comparison of Patient Reported Health Status to start of treatment
  • Change from baseline weight. [ Time Frame: 26 weeks ]
    Comparison of weight from start of treatment until end of treatment


Original Secondary Outcome: Same as current

Information By: Global Alliance for TB Drug Development

Dates:
Date Received: March 7, 2017
Date Started: October 2017
Date Completion: January 2022
Last Updated: March 15, 2017
Last Verified: March 2017