Tuberculosis, Pulmonary, Drug SensitivePhase 3STANDNCT02342886

Shortening Treatment by Advancing Novel Drugs

A Phase 3 study testing Moxifloxacin, PA-824 and Pyrazinamide in people with Tuberculosis, Pulmonary, Drug Sensitive and Tuberculosis, Pulmonary, Multi Drug-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

The purpose of this study is to assess the efficacy, safety and tolerability of a combination of moxifloxacin, PA-824, and pyrazinamide treatments with varying doses and treatment lengths from 4 to 6 months in subjects with drug-sensitive (DS) pulmonary TB compared to standard HRZE treatment. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Tuberculosis, Pulmonary, Drug Sensitive, Tuberculosis, Pulmonary, Multi Drug-resistant
What is being tested?: Moxifloxacin, PA-824 and Pyrazinamide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 284 participants
Where: 26 sitesin 8 countries
Study dates: Feb 2015to May 2018
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
Male or female, aged 18 years or over.
Body weight (in light clothing and no shoes) ≥ 30 kg.
Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease (IUATLD) and World Health Organization (WHO) scale on smear microscopy at the trial laboratory.
Drug-Sensitive TB treatment arms subjects should be:
sensitive to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid) AND

Show all 22Show fewer

either newly diagnosed for TB or have a patient history of being untreated for at least 3 years after cure from a previous episode of TB. If they are entered into the trial due to being sensitive to rifampicin by rapid sputum based test, however on receipt of the rifampicin resistance testing using an indirect susceptibility test in liquid culture this shows they are rifampicin resistant, they will be:
Excluded as late exclusions;
Possibly replaced as determined by the sponsor.
MDR-TB treatment arm subjects should be resistant to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid).
A chest x-ray which in the opinion of the investigator is compatible with pulmonary TB.
Be of non-childbearing potential or using effective methods of birth control, as defined below:
Non-childbearing potential:
Subject - not heterosexually active or practice sexual abstinence; or
Female subject or male subjects 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
Male subject or female subjects male sexual partner - vasectomised or has had a bilateral orchidectomy minimally three months prior to screening;
Effective birth control methods:
Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom; or
Female subject: Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female patient.
Male subjects' female sexual partner: Double barrier method or hormone-based contraceptives or an intra-uterine device for the female partner.
and are willing to continue practising birth control methods and are not planning to conceive throughout treatment and for 12 weeks (male subjects) or 1 week (female subjects) after the last dose of trial medication or discontinuation from trial medication in case of premature discontinuation.
(Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore,

Who cannot join

Any non TB related condition (including myasthenia gravis) where participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments.
Being or about to be treated for Malaria.
Is critically ill and, in the judgment of the investigator, has a diagnosis likely to result in death during the trial or the follow-up period.
TB meningitis or other forms of extrapulmonary tuberculosis with high risk of a poor outcome, or likely to require a longer course of therapy (such as TB of the bone or joint), as judged by the investigator.
History of allergy or hypersensitivity to any of the trial IMP or related substances, including known allergy to any fluoroquinolone antibiotic, history of tendinopathy associated with quinolones or suspected hypersensitivity to any rifampicin antibiotics.
For HIV infected subjects any of the following:

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CD4+ count <100 cells/µL;
Karnofsky score <60%;
Received intravenous antifungal medication within the last 90 days;
WHO Clinical Stage 4 HIV disease.
Resistant to fluoroquinolones (rapid, sputum - based molecular screening tests). If they are entered into the trial due to being sensitive to fluoroquinolones by rapid sputum based test, however on receipt of the fluoroquinolones resistance testing using an indirect susceptibility test in liquid culture this shows they are fluoroquinolones resistant, they will be:
Excluded as late exclusions;
Possibly replaced as determined by the sponsor.
Resistant to pyrazinamide (rapid, sputum - based molecular screening tests).
Drug-Sensitive TB treatment arms subjects may be entered prior to receipt of the rapid, sputum - based molecular pyrazinamide resistance screening test result. On receipt of the result, if they are resistant, they will be:
Excluded as late exclusions;
Possibly replaced as determined by the sponsor. MDR-TB treatment arm subjects may not be entered prior to receipt of the rapid, sputum - based molecular pyrazinamide resistance screening test result showing they are sensitive to pyrazinamide.
Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
Subjects with any of the following at screening (per measurements and reading done by Central Electrocardiogram (ECG) where applicable):
Cardiac arrhythmia requiring medication;
Prolongation of QT/QTc interval with QTcF (Fridericia correction) >450 ms;
History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
Any clinically significant ECG abnormality, in the opinion of the investigator.
Unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-glycaemia within the past year prior to start of screening.
Specific Treatments
Previous treatment with PA-824 as part of a clinical trial.
For DS-TB treatment arms: Previous treatment for tuberculosis within 3 years prior to Day (-9 to -1)(Screening). Subjects who have previously received isoniazid prophylactically may be included in the trial as long as that treatment is/was discontinued at least 7 days prior to randomization into this trial.
For the MDR-TB Subjects: Previous treatment for MDR-TB, although may have been on a MDR TB treatment regimen for no longer than 7 days at start of screening.
Previous treatment for TB includes, but is not limited to, gatifloxacin, amikacin, cycloserine, rifabutin, kanamycin, para-aminosalicylic acid, rifapentine, thioacetazone, capreomycin, quinolones, thioamides, and metronidazole.
Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.
Use of any drug within 30 days prior to randomisation known to prolong QTc interval (including, but not limited to, amiodarone, amitriptyline, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinacrine, quinidine, sotalol, sparfloxacin, thioridazine).
Use of systemic glucocorticoids within one year of start of screening (inhaled or intranasal glucocorticoids are allowed).
Subjects recently started or expected to need to start anti-retroviral therapy (ART) within 1 month after randomization. Subjects may be included who have been on ARTs for greater than 30 days prior to start of screening, or who are expected to start ART greater than 30 days after randomization.
Laboratory Abnormalities
Subjects with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007), where applicable:
creatinine grade 2 or greater (>1.5 times upper limit of normal [ULN]);
creatinine clearance (CrCl) level less than 30 mLs/min according to the Cockcroft-Gault Formula;
haemoglobin grade 4 (<6.5 g/dL);
platelets grade 3 or greater (under 50x109 cells/L/ 50 000/mm3);
serum potassium less than the lower limit of normal for the laboratory. This may be repeated once;
aspartate aminotransferase (AST) grade 3 or greater (≥3.0 x ULN) ;
alanine aminotransferase (ALT) grade 3 or greater (≥3.0 x ULN);
alkaline phosphatase (ALP):
grade 4 (>8.0 x ULN) to be excluded;
grade 3 (≥3.0 - 8.0 x ULN) must be discussed with and approved by the sponsor Medical Monitor;
total bilirubin:
2.0 x ULN, when other liver functions are in the normal range
1.50 x ULN when accompanied by any increase in other liver function tests subjects with total bilirubin > 1.25 x ULN and accompanied by any increase in other liver function tests must be discussed with the sponsor medical monitor before enrollment

Trial locations and contacts

26 sites in 8 countries.

Country

City, postcode or hospital

26 sites in 8 countries

South Africa12 sites

TASK
Bellville, Cape Town, 7531
Madibeng Centre for Research (MCR)
Brits, 0250
Durban International Clinical Trials Unit (DbnlCTU)
Durban, KwaZulu-Natal, 4001
THINK: Tuberculosis & HIV Investigative Network of Kwazulu Natal
Durban, 4001
Klerksdorp Tshepong Hospital
Klerksdorp, North West, 2571
The Aurum Institute
Klerksdorp
Synexus SA
Mamelodi East, Pretoria
University of Cape Town Lung Institute
Mowbray, Cape Town, 7700
Setshaba Research Centre
Pretoria, Gauteng
The Aurum Institute: Rustenberg
Rustenburg
The Aurum Institute: Tembisa Hospital Cnr
Tembisa, Gauteng, 1632
CHRU Themba Lethu Clinic
Westdene, Johannesburg

Other trials in South Africa

Malaysia3 sites

Universiti Teknologi MARA
Batu Caves, Selangor
Pusat Perubatan Universiti Kebangsaan
Cheras, Kuala Lumpur
Institute of Respiratory Medicine (IPR)
Kuala Lumpur, 53000

Other trials in Malaysia

Philippines3 sites

Philippine General Hospital
Ermita, Manila, 1000
Lung Center of Philippines
Manila, 1104
Vincent Balang
Pio del Pilar, Manila, 1230

Other trials in Philippines

Tanzania3 sites

Ifakara Health Institute (IHI)
Dar es Salaam
NIMR - Mbeya Medical Research Programme (MMRP)
Mbeya
Kilimanjaro National Institute for Medical Research
Mwanza

Other trials in Tanzania

Kenya2 sites

Centre for Respiratory Disease Research (CRDR) Keny Medical Research Institute (KEMRI)
Nairobi
Centre for Respiratory Disease Research (CRDR) Kenya Medical Research Institute (KEMRI)
Nairobi

Other trials in Kenya

Georgia1 site

National Center for Tuberculosis and Lung Diseases
Tbilisi, 0101

Other trials in Georgia

Uganda1 site

Uganda CWRU Research Collaboration
Kampala

Other trials in Uganda

Zambia1 site

Centre for Infectious Disease Research in Zambia (CIDRZ)
Lusaka

Other trials in Zambia

About this study

Official title: A Phase 3 Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 4 and 6 Months of Treatment in Adult Subjects With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis and After 6 Months of Treatment in Adult Subjects With Multi-Drug Resistant, Smear-Positive Pulmonary Tuberculosis.

This study will also assess the efficacy, safety and tolerability of a combination of moxifloxacin, PA-824, and pyrazinamide treatments after 6 months of treatment in subjects with multi drug-resistant (MDR) pulmonary TB compared to a combination of moxifloxacin, PA-824, and pyrazinamide treatments in DS-TB subjects.

Conditions: Tuberculosis, Pulmonary, Drug Sensitive, Tuberculosis, Pulmonary, Multi Drug-resistant
Being tested: Moxifloxacin, PA-824, Pyrazinamide, HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination), HR (rifampicin plus isoniazid combination tablets)
Keywords: Tuberculosis, Multi Drug-Resistant Tuberculosis, Drug-sensitive Tuberculosis, PA-824, Moxifloxacin, Pyrazinamide, Rifampicin, Isoniazid, Ethambutol, HRZE, HR, Pretomanid, NC-006, STAND
Medical subject headings: Tuberculosis, Tuberculosis, Multidrug-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MoxifloxacinDrug
Also called BAY 12-8039, Avelox, Avalon, Avelon
Oral
PA-824Drug
Oral
PyrazinamideDrug
Oral
HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination)Drug
Also called Rifafour e-275
Oral
HR (rifampicin plus isoniazid combination tablets)Drug
Oral

Study groups in NCT02342886
Study group	Role	What they receive
MDR-TB	Experimental	moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg for 26 weeks. Receives: Drug: Moxifloxacin; Drug: PA-824; Drug: Pyrazinamide
DS-TB (HRZE), HR	Active comparator	26 consecutive weeks to DS-TB subjects only, as follows: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination) Weeks 1-8 with daily dose per the subjects weight HR (Rifampicin plus isoniazid combination tablets) Weeks 9 - 26 with daily dose per the subjects weight Daily dose per the subjects weight as follows: 30-39kg: 2 tablets; 40-54kg: 3 tablets; 55 - 70kg: 4 tablets; 71kg and over: 5 tablets. Receives: Drug: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination); Drug: HR (rifampicin plus isoniazid combination tablets)
DS-TB PA-824 200mg 26 weeks	Experimental	moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg orally once daily for 26 weeks Receives: Drug: Moxifloxacin; Drug: PA-824; Drug: Pyrazinamide
DS-TB PA-824 200mg 17 weeks	Experimental	moxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg orally once a day for 17 weeks Receives: Drug: Moxifloxacin; Drug: PA-824; Drug: Pyrazinamide
DS-TB PA-824 100mg 17 weeks	Experimental	moxifloxacin 400 mg + PA-824 100 mg + pyrazinamide 1500 mg orally once daily for 17 weeks Receives: Drug: Moxifloxacin; Drug: PA-824; Drug: Pyrazinamide

What is being measured

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

Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Modified Intent to Treat [MITT] Population)
Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy.
A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following end of treatment (EOT), had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or were dying from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required an extension, restart or change of treatment except for reinfection/pregnancy, or failed to complete adequate treatment who were unassessable at 12 months or lost to follow-up/withdrawn before EOT.
Measured: From Day 1 to Month 12.
Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Per Protocol [PP] Population)
Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy.
A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following EOT, had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or died from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required a restart or change of treatment because of an unfavorable outcome with or without bacteriological confirmation, ie, on bacteriological, radiographic or clinical grounds.
Measured: From Day 1 to Month 12.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2015May 2018

First posted21 Jan 2015 (estimated)
Study startFeb 2015
Primary completionJan 2018
Study completionMay 2018

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.
Other trials for Tuberculosis, Pulmonary, Drug SensitiveStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 284 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02342886
Sponsor's protocol ID: NC-006-(M-PA-Z)
Acronym: STAND
Status last verified: Mar 2019
First submitted: 14 Oct 2014
Last updated: 26 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3 Open-Label Partially Randomized Trial to Evaluate the Efficacy, Safety and Tolerability of the Combination of Moxifloxacin Plus PA-824 Plus Pyrazinamide After 4 and 6 Months of Treatment in Adult Subjects With Drug-Sensitive Smear-Positive Pulmonary Tuberculosis and After 6 Months of Treatment in Adult Subjects With Multi-Drug Resistant, Smear-Positive Pulmonary Tuberculosis.
ClinicalTrials.gov ID: NCT02342886
Acronym / sponsor ID: STAND / NC-006-(M-PA-Z)
Conditions: Tuberculosis, Pulmonary, Drug Sensitive, Tuberculosis, Pulmonary, Multi Drug-resistant
Keywords: Tuberculosis, Multi Drug-Resistant Tuberculosis, Drug-sensitive Tuberculosis, PA-824, Moxifloxacin, Pyrazinamide, Rifampicin, Isoniazid
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 284 participants (actual)
Lead sponsor: Global Alliance for TB Drug DevelopmentUniversity, hospital or other
Study start: Feb 2015 (actual)
Primary completion: Jan 2018 (actual)
Study completion: May 2018 (actual)
First posted: 21 Jan 2015 (estimated)
Results: Posted 26 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
MDR-TB	Experimental	Drug: Moxifloxacin, Drug: PA-824, Drug: Pyrazinamidemoxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg for 26 weeks.
DS-TB (HRZE), HR	Active comparator	Drug: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination), Drug: HR (rifampicin plus isoniazid combination tablets)26 consecutive weeks to DS-TB subjects only, as follows: HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination) Weeks 1-8 with daily dose per the subjects weight HR (Rifampicin plus isoniazid combination tablets) Weeks 9 - 26 with daily dose per the subjects weight Daily dose per the subjects weight as follows: 30-39kg: 2 tablets; 40-54kg: 3 tablets; 55 - 70kg: 4 tablets; 71kg and over: 5 tablets.
DS-TB PA-824 200mg 26 weeks	Experimental	Drug: Moxifloxacin, Drug: PA-824, Drug: Pyrazinamidemoxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg orally once daily for 26 weeks
DS-TB PA-824 200mg 17 weeks	Experimental	Drug: Moxifloxacin, Drug: PA-824, Drug: Pyrazinamidemoxifloxacin 400 mg + PA-824 200 mg + pyrazinamide 1500 mg orally once a day for 17 weeks
DS-TB PA-824 100mg 17 weeks	Experimental	Drug: Moxifloxacin, Drug: PA-824, Drug: Pyrazinamidemoxifloxacin 400 mg + PA-824 100 mg + pyrazinamide 1500 mg orally once daily for 17 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
Male or female, aged 18 years or over.
Body weight (in light clothing and no shoes) ≥ 30 kg.
Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease (IUATLD) and World Health Organization (WHO) scale on smear microscopy at the trial laboratory.
Drug-Sensitive TB treatment arms subjects should be:

Key exclusion criteria (48 listed)

Any non TB related condition (including myasthenia gravis) where participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments.
Being or about to be treated for Malaria.
Is critically ill and, in the judgment of the investigator, has a diagnosis likely to result in death during the trial or the follow-up period.
TB meningitis or other forms of extrapulmonary tuberculosis with high risk of a poor outcome, or likely to require a longer course of therapy (such as TB of the bone or joint), as judged by the investigator.
History of allergy or hypersensitivity to any of the trial IMP or related substances, including known allergy to any fluoroquinolone antibiotic, history of tendinopathy associated with quinolones or suspected hypersensitivity to any rifampicin antibiotics.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MoxifloxacinAlso: BAY 12-8039, Avelox, Avalon, AvelonOral	Drug	DS-TB PA-824 100mg 17 weeks, DS-TB PA-824 200mg 17 weeks, DS-TB PA-824 200mg 26 weeks, MDR-TB
PA-824Oral	Drug	DS-TB PA-824 100mg 17 weeks, DS-TB PA-824 200mg 17 weeks, DS-TB PA-824 200mg 26 weeks, MDR-TB
PyrazinamideOral	Drug	DS-TB PA-824 100mg 17 weeks, DS-TB PA-824 200mg 17 weeks, DS-TB PA-824 200mg 26 weeks, MDR-TB
HRZE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol combination)Also: Rifafour e-275Oral	Drug	DS-TB (HRZE), HR
HR (rifampicin plus isoniazid combination tablets)Oral	Drug	DS-TB (HRZE), HR

Primary outcome

Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Modified Intent to Treat [MITT] Population)
Time frame: From Day 1 to Month 12.
Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy. A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following end of treatment (EOT), had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or were dying from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required an extension, restart or change of treatment except for reinfection/pregnancy, or failed to complete adequate treatment who were unassessable at 12 months or lost to follow-up/withdrawn before EOT.
Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Per Protocol [PP] Population)
Time frame: From Day 1 to Month 12.
Patients were classified as having a favorable, unfavorable or unassessable status at 12 months from the start of therapy. A favourable status was a negative culture status at 12 months from start of therapy in patients who had not already been classified as having an unfavorable outcome, and whose last positive culture result was followed by at least 2 negative culture results. Patients with an unfavorable status did not achieve/maintain culture negative status, or previously had culture negative status who following EOT, had 2 positive cultures, or had a positive culture not followed by 2 negative cultures, or died from any cause during treatment (except accidental cause not including suicide), or were dying from TB related causes during follow-up, or required a restart or change of treatment because of an unfavorable outcome with or without bacteriological confirmation, ie, on bacteriological, radiographic or clinical grounds.

Results and safety

Results posted to the registry on 26 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide	65	57
DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	71	63
DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	67	52
DS-TB: 2 Months HRZE / 4 Months HR	68	59
MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	13	10

Primary outcome: Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Modified Intent to Treat [MITT] Population)

Time frame: From Day 1 to Month 12.. Count of participants. Unit: Participants

Measure	DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide n = 57	DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 61	DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 56	DS-TB: 2 Months HRZE / 4 Months HR n = 60	MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 11
Favorable	38	46	43	52	10
Unfavorable	19	15	13	8	1

DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide vs DS-TB: 2 Months HRZE / 4 Months HR: Treatment difference: unfavourable rate: 9.88 (95% CI -4.13 to 23.89)

Population analysed: The MITT population included all randomized patients excluding late screening failures, lost to follow-up/withdrawn patients who were culture negative, pregnancy, accidental death during treatment, death during follow-up without TB relapse evidence, re-infection with new TB strain + missing/contaminated Month 12 sputum sample.

Primary outcome: Incidence of Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Per Protocol [PP] Population)

Time frame: From Day 1 to Month 12.. Count of participants. Unit: Participants

Measure	DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide n = 52	DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 57	DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 47	DS-TB: 2 Months HRZE / 4 Months HR n = 53	MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide n = 10
Favorable	38	46	43	52	10
Unfavorable	14	11	4	1	0

DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide vs DS-TB: 2 Months HRZE / 4 Months HR: Treatment difference: unfavourable rate: 6.62 (95% CI -2.15 to 15.40)

Population analysed: The PP population consisted of the MITT population, excluding patients who were lost to follow-up/withdrawn, had modified/extended treatment for reasons other than unfavourable therapeutic response, did not receive adequate amount of allocated study regimen and patients with major protocol deviations, unless already classified as unfavourable.

Adverse events

Time frame: Treatment emergent adverse events were collected from Day 1 up to and including 14 days after the last administration of trial medication (up to a maximum of 28 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
DS-TB: 4 Months Moxifloxacin + PA-824 (100 mg) + Pyrazinamide	3 of 65 (4.6%)	61 of 65 (93.8%)	4 of 65
DS-TB: 4 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	8 of 71 (11.3%)	62 of 71 (87.3%)	3 of 71
DS-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	8 of 67 (11.9%)	63 of 67 (94%)	3 of 67
DS-TB: 2 Months HRZE/ 4 Months HR	3 of 68 (4.4%)	62 of 68 (91.2%)	2 of 68
MDR-TB: 6 Months Moxifloxacin + PA-824 (200 mg) + Pyrazinamide	3 of 13 (23.1%)	12 of 13 (92.3%)	1 of 13

Limitations and caveats (from the sponsor): Following 3 deaths associated with hepatotoxicity, recruitment was suspended, followed by a partial clinical hold by the United States Food and Drug Association. The hold was removed but the Sponsor permanently stopped recruitment in December 2016.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephen H Gillespie, MD principal investigator

University of St Andrews

26 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 22 inclusion and 48 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 26 Mar 2019. 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, Malaysia, Philippines, Tanzania, Kenya 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 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 26 Mar 2019). 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 Combined Bacteriologic Failure or Relapse or Clinical Failure at Month 12 From Start of Therapy (Day 1) (Modified Intent to Treat [MITT] Population) (time frame: From Day 1 to Month 12.). The study lists 2 primary outcomes in all. 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 NCT02342886.

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 26 Mar 2019.