Tuberculosis, PulmonaryPhase 2/3NCT03338621
Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients
A Phase 2/3 study testing Pretomanid, Bedaquiline and Moxifloxacin in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Global Alliance for TB Drug Development at 26 sites in 8 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR
- What is being tested?
- Pretomanid, Bedaquiline and Moxifloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 455 participants
- Where
- 26 sitesin 8 countries
- Study dates
- 30 Jul 2018to 10 Jun 2022
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease [IUATLD]/WHO scale (Appendix 1) on smear microscopy) at the trial laboratory.
- Participants with one of the following pulmonary TB conditions:
- DS-TB treatment arm participants should be:
- sensitive to rifampicin and isoniazid by rapid sputum based test AND
- either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB.
- DR-TB treatment arm participants should be Resistant to rifampicin and/or isoniazid.
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- Of non-childbearing potential or willing to practice effective methods of birth control
- Body weight (in light clothing and no shoes) ≥ 30 kg.
- Completed informed consent form
Who cannot join
- Karnofsky score <60%
- Any risk factor for QT prolongation
- Any planned contraindicated medicines
- Resistant to fluoroquinolones (rapid, sputum-based molecular screening tests).
- Any of the following lab toxicities/abnormalities:
- CD4+ count < 100 cells/µL (HIV infected participants)
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- platelets <75,000/mm³
- creatinine >1.5 times upper limit of normal (ULN)
- eGFR ≤ 60 mL/min
- haemoglobin <8.0 g/dL
- serum potassium less than the lower limit of normal for the laboratory.
- GGT: greater than 3 x ULN
- AST: ≥3.0 x ULN to be excluded;
- ALT: ≥3.0 x ULN to be excluded
- ALP: ≥3.0 x ULN to be excluded
- Total bilirubin: >1.5 x ULN to be excluded;
- Direct bilirubin: greater than 1x ULN to be excluded
Trial locations and contacts
26 sites in 8 countries.
26 sites in 8 countries
South Africa10 sites
Madibeng Centre for Research
Brits, 0250
TASK
Cape Town, 7530
University of Cape Town Lung Institute
Cape Town, 7700
Enhancing Care Foundation
Durban, 4001
CHRU, King Dinuzulu
Durban, 4015
CHRU, Helen Joseph Hospital
Johannesburg, 2092
PHRU, Tshepong Hospital
Klerksdorp, 2571
THINK
Pietermaritzburg, KwaZulu-Natal, 3216
CHRU, Empilweni TB Hospital
Port Elizabeth, 7070
Setshaba Research Centre
Soshanguve, 0152
Russia5 sites
Moscow City Research and Practice Tuberculosis Treatment Centre
Moscow, 107014
Central TB Research Institute of the Federal Agency of Scientific Organizations
Moscow, 107564
Research Institute of Phthisiopulmonology of I. M. Sechenov First Moscow State Medical University
Moscow, 119991
Research Institute of the Phthisiopulmonology
Saint Petersburg, 191036
Ural Research Institute of Phthisiopulmonology
Yekaterinburg, 620039
Tanzania4 sites
Ifakara Health Institute
Bagamoyo
NIMR-Mbeya
Mbeya
Kilimanjaro Clinical Research Institute
Moshi
Mwanza Intervention Trials Unit
Mwanza, Tanzania
Philippines2 sites
Lung Center of Philippines
Manila, 1104
Tropical Disease Foundation
Manila, 1230
Georgia1 site
National Center for Tuberculosis and Lung Diseases
Tbilisi, K'alak'i T'bilisi, 0101
About this study
Official title: An Open-Label, Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of a 4-month Treatment of Bedaquiline Plus Pretomanid Plus Moxifloxacin Plus Pyrazinamide (BPaMZ) Compared to a 6-month Treatment of HRZE/HR (Control) in Adult Participants With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis (DS-TB) and a 6-month Treatment of BPaMZ in Adult Participants With Drug Resistant, Smear-Positive Pulmonary Tuberculosis (DR-TB)
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)
Read the detailed description
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).
- Conditions
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR, Tuberculosis, Drug-Resistant Tuberculosis
- Being tested
- Pretomanid, Bedaquiline, Moxifloxacin, Pyrazinamide, HRZE
- Keywords
- tuberculosis, drug-resistant tuberculosis, TB, DR-TB, pretomanid, PA-824, bedaquiline, TMC207, moxifloxacin, pyrazinamide, HRZE, TB Alliance, NC-008, drug-sensitive tuberculosis, DS-TB
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PretomanidDrug
Also called PA-824, Pa
200 mg tablets
BedaquilineDrug
Also called B, TMC207
100 mg tablets
MoxifloxacinDrug
Also called M
400 mg tablets
PyrazinamideDrug
Also called Z
500 mg tablets
HRZEDrug
Also called isoniazid, rifampicin, ethambutol
isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets
HRDrug
Also called isoniazid, rifampicin
isoniazid 75 mg plus rifampicin 150 mg combination tablets
| Study group | Role | What they receive |
|---|---|---|
| Drug Sensitive BPaMZ | Experimental | Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months Receives: Drug: Pretomanid; Drug: Bedaquiline; Drug: Moxifloxacin; Drug: Pyrazinamide |
| Drug Sensitive Standard Treatment | Active comparator | isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 Receives: Drug: HRZE; Drug: HR |
| Drug Resistant BPaMZ | Experimental | Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Receives: Drug: Pretomanid; Drug: Bedaquiline; Drug: Moxifloxacin; Drug: Pyrazinamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Days 0-56 (8 weeks)
Secondary outcomes (2)
Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months)
Unfavorable status:
- Participants not classified as having achieved or maintained culture negative status when last seen
- Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture
- Participants who had a positive culture not followed by at least two negative cultures when last seen
- Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide
- Participants definitely or possibly dying from TB related cause during the follow-up phase
- 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
- Participants lost to follow up or withdrawn from the study before end of treatment
Measured: 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
Measured: During treatment (17 or 26 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start30 Jul 2018
- Primary completion1 Jul 2021
- Study completion10 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants
- Masking
- None (open label)
- Enrolment
- 455 participants (actual)
Sponsor and investigators
- Lead sponsor
- Global Alliance for TB Drug Development
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Morounfolu Olugbosi, MD MSc, Study chair, Global Alliance for TB Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03338621
- Sponsor's protocol ID
- SimpliciTB (B-Pa-M-Z) NC-008
- Status last verified
- Mar 2024
- First submitted
- 3 Nov 2017
- Last updated
- 27 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD from the trial will be submitted to Critical Path Institute which will make fully anonymized data available through the Tuberculosis Platform for Aggregation of Clinical TB Studies (TB-PACTS) database. Data sets for Drug susceptibility data, Demographic data, MTB diagnostic testing results, Concomitant medications information, Adverse event information, Treatment adherence information, Co-morbidities, Treatment outcomes, HIV co-infection information, CD4 counts, TB disease symptoms from all collected IPD will be made available.
Publications
Cevik M, Thompson LC, Upton C, Rolla VC, Malahleha M, Mmbaga B, Ngubane N, Abu Bakar Z, Rassool M, Variava E, Dawson R, Staples S, Lalloo U, Louw C, Conradie F, Eristavi M, Samoilova A, Skornyakov SN, Ntinginya NE, Haraka F, Praygod G, Mayanja-Kizza H, Caoili J, Balanag V, Dalcolmo MP, McHugh T, Hunt R, Solanki P, Bateson A, Crook AM, Fabiane S, Timm J, Sun E, Spigelman M, Sloan DJ, Gillespie SH; SimpliciTB Consortium. Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial. Lancet Infect Dis. 2024 Sep;24(9):1003-1014. doi: 10.1016/S1473-3099(24)00223-8. Epub 2024 May 17.
PubMed 38768617