Clinical Trial: A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Pulmonary Infection of Either Extensively Drug-resistant T

Brief Summary: The purpose of this study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of bedaquiline plus PA-824 plus linezolid after 6 months of treatment (option for 9 months for subjects who remain culture positive at month 4) in Subjects with either pulmonary extensively drug resistant tuberculosis (XDR-TB), treatment intolerant or non-responsive multi-drug resistant tuberculosis (MDR-TB).

Detailed Summary:
Sponsor: Global Alliance for TB Drug Development

Current Primary Outcome: Incidence of bacteriologic failure or relapse or clinical failure through follow up until 24 months after the end of treatment. [ Time Frame: Treatment Period: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39 Follow Up: Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]

Bacteriologic failure: During the treatment period, failure to attain culture conversion to negative.

Bacteriologic relapse: During the follow-up period, failure to maintain culture conversion to negative status in culture, with culture conversion to positive status with a Mycobacterium tuberculosis (M.tb.) strain that is genetically identical to the infecting strain at baseline.

Clinical failure: A change from protocol-specified TB treatment due to treatment failure, retreatment for TB during follow up, or TB-related death.

Note:

Culture conversion requires at least 2 consecutive culture negative/positive samples at least 21 days apart.

Subjects who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.



Original Primary Outcome: Incidence of bacteriologic failure or relapse or clinical failure through follow up until 24 months after the end of treatment. [ Time Frame: Treatment Period: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39 Follow Up: Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]

Bacteriologic failure: During the treatment period, failure to attain culture conversion to negative.

Bacteriologic relapse: During the follow-up period, failure to maintain culture conversion to negative status in culture, with culture conversion to positive status with a of Mycobacterium tuberculosis (M.tb.) strain that is genetically identical to the infecting strain at baseline.

Clinical failure: A change from protocol-specified TB treatment due to treatment failure, retreatment for TB during follow up, or TB-related death.

Note:

Culture conversion requires at least 2 consecutive culture negative/positive samples at least 21 days apart.

Subjects who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.



Current Secondary Outcome:

  • Time to sputum culture conversion to negative status through the treatment period. [ Time Frame: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]
  • Proportion of subjects with sputum culture conversion to negative status at 4, 6, 8, 12, 16 and 26 or 39 weeks. [ Time Frame: Week 4, 6, 8, 12, 16, 26, 39 ]
  • Incidence of Treatment Emergent Adverse Events (TEAEs) presented by incidence, and seriousness, leading to TB related or non-TB related death. [ Time Frame: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39, Follow-up Month 3, 6, 9, 12, 15, 18, 21, 24 ]
  • All Subjects- Pre-dose sampling at weeks 2, 8 and 16 to measure Ctrough levels of bedaquiline, bedaquiline metabolite M2, Linezolid and PA-824. [ Time Frame: Weeks 2, 8 and 16 ]
  • Time to sputum culture positivity [ Time Frame: Treatment Period: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39 Follow Up: Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]
    If liquid culture in the MGIT platform is used, the rate of change in time to sputum culture positivity (TTP) over time in the Mycobacterial Growth Indicator Tube (MGIT) system in sputum, represented by the model-fitted log(TTP) results as calculated by the regression of the observed log(TTP) results over time.


Original Secondary Outcome: Same as current

Information By: Global Alliance for TB Drug Development

Dates:
Date Received: January 6, 2015
Date Started: March 2015
Date Completion: October 2021
Last Updated: February 28, 2017
Last Verified: August 2016