NCT03086486

Various Doses and Durations of Linezolid Plus Bedaquiline & Pretomanid in Participants With Drug Resistant Tuberculosis

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 Infection of Either Extensively Drug-resistant Tuberculosis (XDR-TB), Pre-XDR-TB or Treatment Intolerant or Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 181 (actual)
• Sponsor: Global Alliance for TB Drug Development · Academic / Other
• Sex: All
• Age: 14 Years
• Healthy volunteers: Not accepted

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 description

A phase 3, multi-center, partially-blinded, randomized clinical trial in 4 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 14 days and will be randomized to receive one of the 4 active treatment arms. Participants will be randomized to one of the 4 regimens in a 1:1:1:1 ratio, using an interactive voice and web response system (IXRS) which will utilize a randomization system using stratification 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 sputum sample is culture positive between the week 16 and week 26 treatment visits and their clinical condition suggests they may have an ongoing TB infection, Investigator may consider extending current treatment to 39 weeks. If the culture results between week 16 and week 26 are contaminated, missing or considered an isolated positive without clinical significance, available culture results should be used to make this decision. All decisions regarding treatment extension should be discussed with and approved by, in consultation with the Sponsor Medical Monitor before implementation. The treatment may also require modification due to toxicities. All dose modifications should be discussed with the Sponsor Medical Monitor prior to implementation, unless a pause or dose reduction is required urgently for safety concerns. Participants will be followed for 78 weeks after end of treatment.

Conditions

• Tuberculosis, Pulmonary
• Tuberculosis, Multidrug-Resistant
• Tuberculosis, MDR
• Tuberculosis
• Extensively Drug-Resistant Tuberculosis
• Pre-XDR-TB
• XDR-TB

Interventions

Type	Name	Description
DRUG	Pretomanid	200mg tablets
DRUG	Linezolid	Scored 600mg tablets
DRUG	Bedaquiline	100mg tablets
DRUG	Placebo Linezolid	Scored 600 mg tablets

Timeline

• Start date: 2017-11-21
• Primary completion: 2021-02-15
• Completion: 2022-02-08
• First posted: 2017-03-22
• Last updated: 2023-06-29
• Results posted: 2023-06-29

Locations

11 sites across 4 countries: Georgia, Moldova, Russia, South Africa

Regulatory

• FDA-regulated drug study