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Tuberculosis, PulmonaryPhase 3ZeNixNCT03086486

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

A Phase 3 study testing Pretomanid, Linezolid and Bedaquiline in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Global Alliance for TB Drug Development at 11 sites in 4 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 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. Read more about this study

Who is it for?
Ages 14 years and older
What is being tested?
Pretomanid, Linezolid and Bedaquiline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
181 participants
Where
11 sitesin 4 countries
Study dates
21 Nov 2017to 8 Feb 2022
Phase
Phase 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 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male or female, aged 14 years or older.
  • One of the following with documentation of culture positive or molecular test within 3 months of screening:
  • XDR-TB defined as resistance to rifamycins, a fluoroquinolone AND an injectable OR
  • Pre-XDR-TB with defined as resistance to rifamycins, and to a fluoroquinolone OR an injectable OR
  • MDR-TB with resistance to rifamycins, and either non-responsive or non-tolerant to current treatment.
  • Of non-childbearing potential or willing to practice effective birth control methods.
  • Complete informed consent form.

Who cannot join

  • Karnofsky score < 60 at screening.
  • Body mass index (BMI) < 17 kg/m2
  • Participants who are expected to require a surgical procedure (for Pulmonary TB).
  • Any risk factor for QT prolongation
  • Pregnant or breast-feeding
  • Any planned contraindicated medicines or received more than 2 weeks of bedaquiline, linezolid or delamanid prior to first dose of IMP.
Show all 19Show fewer
  • A peripheral neuropathy of Grade 3 or 4, according to DMID. Or, participants with a Grade 1 or 2 neuropathy which is likely to progress/worsen over the course of the study, in the opinion of the Investigator
  • Any of the following lab toxicities/abnormalities:
  • Viral load >1000 copies/mL (Unless newly diagnosed HIV and not yet on ART who otherwise qualify for participation);
  • CD4+ count < 100 cells/µL (HIV positive participants);
  • Serum potassium less than the lower limit of normal for the laboratory;
  • Hemoglobin < 9.0 g/dL or 90g/L;
  • Platelets <100,000/mm3 or < 100 x 10^9/L
  • Absolute neutrophil count (ANC) < 1500/ mm3 or < 1.5 x 10^9/L
  • Aspartate aminotransferase (AST) and Alanini aminotransferase (ALT) Grade 3 or greater (> 3.0 x ULN)
  • Total bilirubin greater than 1.5 x ULN
  • Direct bilirubin greater than ULN
  • Serum creatinine level greater than 1.5 times upper limit of normal
  • Albumin <3.0 g/dl or < 30 g/L

Trial locations and contacts

11 sites in 4 countries.

11 sites in 4 countries

Russia5 sites

  • Moscow City Research and Practice Tuberculosis Treatment Centre

    Moscow, 107014

  • Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow

    Moscow, 107564

  • National Medical Research Center of Phthisiopulmonology and Infectious Diseases

    Moscow

  • FSBI "Saint-Petersburg Research Institute of Phthisiopulmonology"

    Saint Petersburg, 191036

  • Ural Research Institute of Phthisiopulmonology

    Yekaterinburg, 620039

Other trials in Russia

South Africa4 sites

  • King DinuZulu Hospital Complex

    Durban, 4015

  • Clinical HIV Research Unit (CHRU) Sizwe Tropical Diseases Hospital

    Johannesburg, 2131

  • Tshepong Hospital

    Klerksdorp, North West, 2574

  • Empilweni TB Hospital

    Port Elizabeth, Eastern Cape

Other trials in South Africa

Georgia1 site

  • National Center for Tuberculosis and Lung Diseases

    Tbilisi, 0101

Other trials in Georgia

Moldova1 site

  • Institute of Phthisiopneumology Chiril Draganiuc

    Chisinau, 2025

Other trials in Moldova

About this study

Official title: 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)

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.

Read the 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.

Being tested
Pretomanid, Linezolid, Bedaquiline, Placebo Linezolid
Keywords
Tuberculosis, Multi Drug-Resistant Tuberculosis, Extensively Drug-Resistant Tuberculosis, Drug-Resistant Tuberculosis, Pretomanid, PA-824, Bedaquiline, Linezolid, NC-007, TB Alliance, pre-XDR-TB, Sirturo, Zyvox, ZeNix
Medical subject headings
Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, Extensively Drug-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

    200mg tablets

  • LinezolidDrug

    Also called L, Lin, Zyvox

    Scored 600mg tablets

  • BedaquilineDrug

    Also called TMC-207, B, Sirturo

    100mg tablets

  • Placebo LinezolidDrug

    Scored 600 mg tablets

Study groups in NCT03086486
Study groupRoleWhat they receive
1200mg L x 26 weeks + Pa + BExperimental2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
Receives: Drug: Pretomanid; Drug: Linezolid; Drug: Bedaquiline; Drug: Placebo Linezolid
1200 mg L x 9 weeks + Pa + BExperimental2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
Receives: Drug: Pretomanid; Drug: Linezolid; Drug: Bedaquiline; Drug: Placebo Linezolid
600 mg L x 26 weeks + Pa + BExperimental1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
Receives: Drug: Pretomanid; Drug: Linezolid; Drug: Bedaquiline; Drug: Placebo Linezolid
600 mg L x 9 weeks + Pa + BExperimental1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
Receives: Drug: Pretomanid; Drug: Linezolid; Drug: Bedaquiline; Drug: Placebo Linezolid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment

    Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB
    8. Participants lost to follow up or withdrawn from the study before the end of treatment

    Measured: 26 weeks

Secondary outcomes (3)

  1. Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.

    Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB
    8. Participants lost to follow up or withdrawn from the study before the end of treatment

    Measured: 78 weeks

  2. Time to Sputum Culture Conversion to Negative Status Through the Treatment Period

    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures.

    Note:

    • Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart.
    • Participants 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.

    Measured: 26 weeks

  3. Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline

    Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures.

    Measured: End of Treatment, 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 posted22 Mar 2017
  2. Study start21 Nov 2017
  3. Primary completion15 Feb 2021
  4. Study completion8 Feb 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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
181 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03086486
Sponsor's protocol ID
ZeNix (B-Pa-L) NC-007
Acronym
ZeNix
Status last verified
Jun 2023
First submitted
7 Mar 2017
Last updated
29 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bruning-Barry R, Ambroso JL, Yang X, Hickman D, Harkins AM, Noble M, Paris M, Foraida S, Sun E, Beumont M. Safety evaluation of pretomanid, an anti-tuberculosis drug, for the treatment of pregnant and lactating women. Antimicrob Agents Chemother. 2026 Aug 5;70(8):e0034326. doi: 10.1128/aac.00343-26. Epub 2026 Jul 10.

    PubMed 42429813

  • Conradie F, Bagdasaryan TR, Borisov S, Howell P, Mikiashvili L, Ngubane N, Samoilova A, Skornykova S, Tudor E, Variava E, Yablonskiy P, Everitt D, Wills GH, Sun E, Olugbosi M, Egizi E, Li M, Holsta A, Timm J, Bateson A, Crook AM, Fabiane SM, Hunt R, McHugh TD, Tweed CD, Foraida S, Mendel CM, Spigelman M; ZeNix Trial Team. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med. 2022 Sep 1;387(9):810-823. doi: 10.1056/NEJMoa2119430.

    PubMed 36053506

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pretomanid, Linezolid and Bedaquiline in people with Tuberculosis, Pulmonary and Tuberculosis, Multidrug-Resistant, run by Global Alliance for TB Drug Development at 11 sites in 4 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 7 inclusion and 19 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 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Russia, South Africa, Georgia, Moldova. 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 phase mean?

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 29 Jun 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?

Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment (time frame: 26 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 NCT03086486, which also lists 2 linked publications.

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 29 Jun 2023.

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