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

Primary Purpose

Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pretomanid
Linezolid
Bedaquiline
Placebo Linezolid
Sponsored by
Global Alliance for TB Drug Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis, Pulmonary focused on measuring 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

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants are required to meet all of the following inclusion criteria during the screening period in order to be randomized.

  1. Provide written, informed consent prior to all trial-related procedures (including any additional consent required for participants considered as minors per applicable regulatory authority or ethics committee).
  2. Willingness and ability to attend scheduled follow-up visits and undergo study assessments.
  3. HIV testing (if an HIV test was performed within 1 month prior to screening, it should not be repeated as long as a documented result can be provided [ELISA and/or Western Blot and/or Electro-Chemiluminescence]. If HIV status is a confirmed known positive, repeated HIV test is not needed if ELISA and/or Western Blot and/or Electro-Chemiluminescence documentation of presence of HIV infection is available.
  4. Male or female, aged 14 years or older. (Male or female, aged 18 years or older in Moldova or Russia).

    Disease Characteristics:

  5. Participants with one of the following pulmonary TB conditions:

    a. XDR-TB with i. A documented culture positive or a molecular test positive (for MTB) from a sputum specimen collected within 3 months prior to screening or MTB confirmed in sputum based on molecular test within 3 months prior to or at screening and: ii. documented resistance to rifamycins, a fluoroquinolone AND an injectable during the current TB diagnosis/disease course any time prior to or during screening period (may be sensitive or resistant to isoniazid);

    b. Pre-XDR-TB with i. A documented culture positive or a molecular test positive (for MTB) from a sputum specimen collected within 3 months prior to screening or MTB confirmed in sputum based molecular test within 3 months prior to or at screening and; ii. documented resistance to rifamycins, and to a fluoroquinolone OR an injectable during the current TB diagnosis/disease course any time prior to or during screening period (may be sensitive or resistant to isoniazid);

    c. MDR-TB with i. documented by culture positive or a molecular test positive (for MTB) from a sputum specimen collected results within 3 months prior to screening or MTB confirmed in sputum based on molecular test within 3 months prior to or at screening and; ii. documented resistance to rifamycins, and to a fluoroquinolone OR an injectable during the current TB diagnosis/disease course any time prior to or during screening period (may be sensitive or resistant to isoniazid) and; iii. with documented non-response to treatment with the best available regimen for 6 months or more prior to enrollment who in the opinion of the Investigator have been adherent to treatment and will be adherent to study regimen.

    d. MDR-TB with i. documented by culture positive or a molecular test positive (for MTB) from a sputum specimen collected within 3 months prior to screening or MTB confirmed in sputum based on molecular test within 3 months prior to or at screening and: ii. documented resistance to rifamycins during the current TB diagnosis/disease course any time prior to or during screening period (may be sensitive or resistant to isoniazid) and; iii. who are unable to continue second line drug regimen due to a documented intolerance to:

    1. PAS, ethionamide, aminoglycosides or fluoroquinolones or;
    2. Current treatment not listed above that renders participant eligible for the study in the Investigator's opinion.
  6. Chest X-Ray within 6 months prior to or at screening, obtained and read locally by investigator or designee with results consistent with pulmonary TB in the opinion of the Investigator.

    Contraception:

  7. Be of non-childbearing potential or using effective methods of birth control, as defined below:

Non-childbearing potential:

  1. Participant - not heterosexually active or practices sexual abstinence; or
  2. Female participant or male participant's female /sexual partner - bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy or has been postmenopausal with a history of no menses for at least 12 consecutive months; or
  3. Male participant or female participant's male /sexual partner - vasectomised or has had a bilateral orchidectomy at least three months prior to screening.

Effective birth control methods:

  1. Double barrier method which can include: a male condom, diaphragm, cervical cap, or female condom; or
  2. Female participant: Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female participant;
  3. Male participant's female sexual partner: Double barrier method or hormone based contraceptives or an intra-uterine device for the female partner.

And are willing to continue practicing birth control methods throughout treatment and for 6 months (female participants) and 12 weeks (male participants) after the last dose of study medication.

Exclusion Criteria:

Participants will be excluded from participation if they meet any of the following criteria during the screening period:

Medical History and Concurrent Conditions

  1. Any condition in the Investigator's opinion (i.e., an unstable disease such as uncontrolled diabetes or cardiomyopathy, extra-pulmonary TB requiring extended treatment, cancer that could affect survival through the protocol-specified follow up period), where participation in the trial would compromise the well-being of participant or prevent, limit or confound protocol specified assessments.
  2. Abuse of alcohol or illegal drugs that in the opinion of the Investigator would compromise the participants' safety or ability to follow through with all protocol-specified restrictions, visits and evaluations.
  3. In the judgment of the Investigator, the patient is not expected to survive for more than 6 months.
  4. Karnofsky score < 60 at screening.
  5. History of allergy or known hypersensitivity to any of the trial Investigational Medicinal Products or related substances.
  6. Body mass index (BMI) < 17 kg/m2
  7. TB infection with historic DST or MIC results with values suggesting likely resistance to pretomanid, delamanid, linezolid or bedaquiline.; the Sponsor Medical Monitor must be consulted to help interpret any available historic results.
  8. Participants who, upon the evaluation of their pulmonary disease, are expected to require a surgical procedure.
  9. Having participated in other clinical studies with dosing of investigational agents within 8 weeks prior to screening or currently enrolled in an investigational study that includes treatment with medicinal agents. Participants who are participating in observational studies or who are in a follow up period of a trial that included drug therapy may be considered for inclusion.
  10. Participants with any of the following at Screening:

    • QTcF interval on ECG >500 msec. Participants with QTcF > 450 must be discussed with and approved by the Sponsor Medical Monitor before enrollment. (Per measurements and reading done from screening central ECG.)
    • Heart failure
    • A personal or family history of congenital QT prolongation
    • A history of or known, untreated, ongoing hypothyroidism
    • A history of or ongoing bradyarrhythmia
    • A history of Torsade de Pointe
  11. (Russia only) Participants with any of the following conditions where the use of linezolid is contraindicated:

    • A history of thyrotoxicosis
    • A history of uncontrolled arterial hypertension
    • A history of pheochromocytoma
    • A history of carcinoid syndrome
    • A history of bipolar disorder
    • A history of schizoaffective disorder
  12. Females who have a positive pregnancy test at Screening or already known to be pregnant, breast-feeding, or planning to conceive a child during the study or within 6 months of cessation of treatment. Males planning to conceive a child during the study or within 6 months of cessation of treatment.
  13. 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.
  14. (Russia only) Participants with lactose intolerance, lactase deficiency and/or glucose-galactose malabsorption.

    Previous and Concomitant Therapy

  15. Known (during screening) requirement for future Concomitant (during treatment) use of any prohibited and/or avoided medications noted in section 5.3.
  16. Prior use of Monoamine Oxidase Inhibitors (MAOIs) within 2 weeks of randomization.
  17. Prior use of serotonergic antidepressants within 3 days of randomization if Investigator foresees potential risks for serotonin syndrome when combined with linezolid.
  18. Participants who have received more than 2 weeks of bedaquiline, linezolid or delamanid prior to first dose of IMP.
  19. Participants with newly diagnosed tuberculosis and HIV that require initiation of appropriate HIV therapy before participant has received at least 2 weeks of an anti-tuberculosis regimen.
  20. HIV infected participants with planned continued use of zidovudine, stavudine, or didanosine. The antiretroviral therapy (ART) booster cobicistat should not be used.

    Diagnostic and Laboratory Abnormalities

  21. Participants with any of the following toxicities at Screening (labs may be repeated during screening period) as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):

    1. Viral load >1000 copies/mL (Unless newly diagnosed HIV and not yet on ART who otherwise qualify for participation);
    2. CD4+ count < 100 cells/µL (HIV positive participants);
    3. Serum potassium less than the lower limit of normal for the laboratory;
    4. Hemoglobin < 9.0 g/dL or 90g/L;
    5. Platelets <100,000/mm3 or < 100 x 10^9/L ;
    6. Absolute neutrophil count (ANC) < 1500/ mm3 or < 1.5 x 10^9/L;
    7. Aspartate aminotransferase (AST)

      • Grade 3 or greater (> 3.0 x ULN) to be excluded;
      • Results between 1.5 x ULN and 3 x ULN must be discussed with and approved by the Sponsor Medical Monitor
    8. Alanine aminotransferase

      • Grade 3 or greater (> 3.0 x ULN) to be excluded;
      • Results between 1.5 x ULN and 3 x ULN must be discussed with and approved by the Sponsor medical monitor;
    9. Total bilirubin

      • greater than 1.5 x ULN to be excluded;
      • 1-1.5 x ULN must be discussed with and approved by the Sponsor Medical Monitor
    10. Direct bilirubin

      • Greater than ULN to be excluded

    11. Serum creatinine level greater than 1.5 times upper limit of normal
    12. Albumin <3.0 g/dl or < 30 g/L

All inclusion and no exclusion criteria must be met. If no single variable/value is outside of the ranges of acceptability, but when multiple values are close to the limits and/or whenever the Investigator has reason to suspect that there might be a health problem (other than TB), enrolment should only be considered after discussing the case with the sponsor medical monitor.

Sites / Locations

  • National Center for Tuberculosis and Lung Diseases
  • Institute of Phthisiopneumology Chiril Draganiuc
  • Moscow City Research and Practice Tuberculosis Treatment Centre
  • Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow
  • National Medical Research Center of Phthisiopulmonology and Infectious Diseases
  • FSBI "Saint-Petersburg Research Institute of Phthisiopulmonology"
  • Ural Research Institute of Phthisiopulmonology
  • Empilweni TB Hospital
  • Tshepong Hospital
  • King DinuZulu Hospital Complex
  • Clinical HIV Research Unit (CHRU) Sizwe Tropical Diseases Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

1200mg L x 26 weeks + Pa + B

1200 mg L x 9 weeks + Pa + B

600 mg L x 26 weeks + Pa + B

600 mg L x 9 weeks + Pa + B

Arm Description

2 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

2 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

1 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

1 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

Outcomes

Primary Outcome Measures

Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment
Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB Participants lost to follow up or withdrawn from the study before the end of treatment

Secondary Outcome Measures

Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.
Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB Participants lost to follow up or withdrawn from the study before the end of treatment
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.
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.

Full Information

First Posted
March 7, 2017
Last Updated
June 12, 2023
Sponsor
Global Alliance for TB Drug Development
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1. Study Identification

Unique Protocol Identification Number
NCT03086486
Brief Title
Various Doses and Durations of Linezolid Plus Bedaquiline & Pretomanid in Participants With Drug Resistant Tuberculosis
Acronym
ZeNix
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
November 21, 2017 (Actual)
Primary Completion Date
February 15, 2021 (Actual)
Study Completion Date
February 8, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Global Alliance for TB Drug Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR, Tuberculosis, Extensively Drug-Resistant Tuberculosis, Pre-XDR-TB, XDR-TB
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Participants, trial investigators and staff, including laboratory staff, will be blinded to dose and scheduled duration of linezolid. Bedaquiline and pretomanid dosing will not be blinded. There will be three unblinded analyses which will contain results by linezolid treatment group in aggregate. The first analysis will be after all participants have completed 26 weeks of treatment and here sites, participants, and Sponsor staff will not be unblinded to individual linezolid treatment information. A limited number of statisticians will have access to individual linezolid treatment assignments. The blind for all individual participants will be broken for the primary endpoint analysis (the second unblinded analysis) once all clinical data and outcome parameters have been captured, no more data queries are pending, and the statistical analysis plan has been finalized. The third analysis will occur when all participants have completed 78 weeks of follow-up after end of treatment.
Allocation
Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1200mg L x 26 weeks + Pa + B
Arm Type
Experimental
Arm Description
2 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
Arm Title
1200 mg L x 9 weeks + Pa + B
Arm Type
Experimental
Arm Description
2 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
Arm Title
600 mg L x 26 weeks + Pa + B
Arm Type
Experimental
Arm Description
1 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
Arm Title
600 mg L x 9 weeks + Pa + B
Arm Type
Experimental
Arm Description
1 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
Intervention Type
Drug
Intervention Name(s)
Pretomanid
Other Intervention Name(s)
PA-824, Pa
Intervention Description
200mg tablets
Intervention Type
Drug
Intervention Name(s)
Linezolid
Other Intervention Name(s)
L, Lin, Zyvox
Intervention Description
Scored 600mg tablets
Intervention Type
Drug
Intervention Name(s)
Bedaquiline
Other Intervention Name(s)
TMC-207, B, Sirturo
Intervention Description
100mg tablets
Intervention Type
Drug
Intervention Name(s)
Placebo Linezolid
Intervention Description
Scored 600 mg tablets
Primary Outcome Measure Information:
Title
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment
Description
Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB Participants lost to follow up or withdrawn from the study before the end of treatment
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.
Description
Unfavourable 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 who have had surgery and the resected tissue is cultured and is positive for MTB Participants lost to follow up or withdrawn from the study before the end of treatment
Time Frame
78 weeks
Title
Time to Sputum Culture Conversion to Negative Status Through the Treatment Period
Description
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.
Time Frame
26 weeks
Title
Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline
Description
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.
Time Frame
End of Treatment, 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion criteria: 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesca Conradie
Organizational Affiliation
Isango Lethemba TB Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Center for Tuberculosis and Lung Diseases
City
Tbilisi
ZIP/Postal Code
0101
Country
Georgia
Facility Name
Institute of Phthisiopneumology Chiril Draganiuc
City
Chisinau
ZIP/Postal Code
2025
Country
Moldova, Republic of
Facility Name
Moscow City Research and Practice Tuberculosis Treatment Centre
City
Moscow
ZIP/Postal Code
107014
Country
Russian Federation
Facility Name
Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow
City
Moscow
ZIP/Postal Code
107564
Country
Russian Federation
Facility Name
National Medical Research Center of Phthisiopulmonology and Infectious Diseases
City
Moscow
Country
Russian Federation
Facility Name
FSBI "Saint-Petersburg Research Institute of Phthisiopulmonology"
City
Saint Petersburg
ZIP/Postal Code
191036
Country
Russian Federation
Facility Name
Ural Research Institute of Phthisiopulmonology
City
Yekaterinburg
ZIP/Postal Code
620039
Country
Russian Federation
Facility Name
Empilweni TB Hospital
City
Port Elizabeth
State/Province
Eastern Cape
Country
South Africa
Facility Name
Tshepong Hospital
City
Klerksdorp
State/Province
North - West
ZIP/Postal Code
2574
Country
South Africa
Facility Name
King DinuZulu Hospital Complex
City
Durban
ZIP/Postal Code
4015
Country
South Africa
Facility Name
Clinical HIV Research Unit (CHRU) Sizwe Tropical Diseases Hospital
City
Johannesburg
ZIP/Postal Code
2131
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36053506
Citation
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.
Results Reference
derived

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

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