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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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.
Show all 9Show fewer
  • 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)
Show all 17Show fewer
  • 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

Other trials in South Africa

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

Other trials in Russia

Tanzania4 sites

  • Ifakara Health Institute

    Bagamoyo

  • NIMR-Mbeya

    Mbeya

  • Kilimanjaro Clinical Research Institute

    Moshi

  • Mwanza Intervention Trials Unit

    Mwanza, Tanzania

Other trials in Tanzania

Brazil2 sites

  • Evandro Chagas

    Rio de Janeiro

  • FIOCRUZ

    Rio de Janeiro

Other trials in Brazil

Philippines2 sites

  • Lung Center of Philippines

    Manila, 1104

  • Tropical Disease Foundation

    Manila, 1230

Other trials in Philippines

Georgia1 site

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi, K'alak'i T'bilisi, 0101

Other trials in Georgia

Malaysia1 site

  • Institut Perubatan Respiratori

    Kuala Lumpur

Other trials in Malaysia

Uganda1 site

  • Case Western Reserve University

    Kampala, 2109

Other trials in Uganda

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).

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 groups in NCT03338621
Study groupRoleWhat they receive
Drug Sensitive BPaMZExperimentalBedaquiline 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 TreatmentActive comparatorisoniazid 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 BPaMZExperimentalBedaquiline 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.

  1. 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)

  1. 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

    Measured: 52 weeks after start of therapy

  2. 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.

  1. First posted9 Nov 2017
  2. Study start30 Jul 2018
  3. Primary completion1 Jul 2021
  4. Study completion10 Jun 2022

Resources

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)
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
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in South Africa, Russia, Tanzania, Brazil, Philippines and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Culture Negative Status by 8 Weeks (time frame: Days 0-56 (8 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03338621, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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