A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis
|ClinicalTrials.gov Identifier: NCT02333799|
Recruitment Status : Active, not recruiting
First Posted : January 7, 2015
Last Update Posted : January 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Tuberculosis||Drug: Bedaquiline Drug: PA-824 Drug: Linezolid||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Tuberculosis (XDR-TB) or Treatment Intolerant / Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB).|
|Study Start Date :||March 2015|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2021|
Experimental: Bedaquiline + PA-824 + Linezolid
bedaquiline 400 mg once daily for 2 weeks then 200mg 3 times per week plus PA-824 200mg once daily plus linezolid 600mg twice daily.
Other Names:Drug: PA-824
Other Names:Drug: Linezolid
Scored 600mg tablets
- 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.
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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02333799
|Task Applied Science - Brooklyn Chest Hospital|
|Ysterplaat, Cape Town, South Africa, 7405|
|Sizwe Tropical Disease Hospital|
|Sandringham, Johannesburg, South Africa, 2131|
|THINK: Tuberculosis & HIV Investigative Network of KwaZulu-Natal (Durban)|
|Pietermaritzburg, Kwazulu-Natal, South Africa, 3200|
|Principal Investigator:||Dan Everitt||Global Alliance for TB Drug Development|
|Principal Investigator:||Francesca Conradie||CHRU Themba Lethu Clinic - Helen Joseph Hospital|