To evaluate the efficacy, safety and tolerability at 8 weeks (2-months), 52 weeks (12-months), and 104 Weeks (24-months) post the start of the following treatment regimens in participants with: Drug Sensitive TB (DS-TB) patients given BPaMZ for 17 Weeks ( or 4 months) vs. Standard HRZE/HR treatment given for 26 weeks (or 6 months) and Drug Resistant TB (DR-TB) patients given BPaMZ for 26 Weeks (or 6 months)
Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants. All participants in the below arms will have follow-up for a period of 104 weeks (24 months) from the start of therapy. Participants with Drug Sensitive TB (DS-TB): Participants with DS-TB will be randomized to one of two treatment arms. These participants will receive either BPaMZ daily for 17 weeks (4 months), or HRZE/HR combination tablets daily for 26 weeks (6 months). participants will be stratified for co-infection with human immunodeficiency virus (HIV) and cavitation. Participants with Drug Resistant TB (DR-TB): Participants with DR-TB will be assigned to receive BPaMZ daily for 26 weeks (6 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
455
200 mg tablets
100 mg tablets
400 mg tablets
500 mg tablets
isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets
isoniazid 75 mg plus rifampicin 150 mg combination tablets
Evandro Chagas
Rio de Janeiro, Brazil
FIOCRUZ
Rio de Janeiro, Brazil
National Center for Tuberculosis and Lung Diseases
Tbilisi, Georgia
Institut Perubatan Respiratori
Kuala Lumpur, Malaysia
Lung Center of Philippines
Manila, Philippines
Tropical Disease Foundation
Manila, Philippines
Moscow City Research and Practice Tuberculosis Treatment Centre
Moscow, Russia
Central TB Research Institute of the Federal Agency of Scientific Organizations
Moscow, Russia
Research Institute of Phthisiopulmonology of I. M. Sechenov First Moscow State Medical University
Moscow, Russia
Research Institute of the Phthisiopulmonology
Saint Petersburg, Russia
...and 16 more locations
Number of Participants With Culture Negative Status by 8 Weeks
Culture negative status is achieved when a participant produces at least two negative culture results at different visits (at least 7 days apart) without an intervening positive culture result for M.tb.
Time frame: Days 0-56 (8 weeks)
Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months)
Unfavorable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants lost to follow up or withdrawn from the study before end of treatment
Time frame: 52 weeks after start of therapy
Time to Culture Negative Status
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, that point is considered culture negativity
Time frame: During treatment (17 or 26 weeks)
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