Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
390 participants
INTERVENTIONAL
2023-04-14
2027-12-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
In stage 1, participants will be randomly allocated to the control or one of the 2 rifampicin-containing experimental regimens in the ratio 1:1:1.
In stage 2, the experimental arm 4 containing BTZ-043 will be added. The allocation ratio will be changed to co-enrol the remaining participants in arms 1- 3 simultaneously with arm 4 in a ratio of 1:1:1:2. When arms 1-2 are fully enrolled and arm 4 is not, further participants will be randomized 1:1 to control and experimental arm 4. Not all countries will participate in stage 2.
In stage 3, participants will be allocated in parallel to control arm treatment (now designated arm 7) or the experimental arms 5 and 6, favouring arm 5, 2:1:1 over arms 6 and control. This stage will start after completion of recruitment in the stages 1 and 2. Enrolment of participants into arm 5 will proceed following review of data from the ENABLE/UNITE-03 (NCT06748937), non-clinical safety data and after endorsement by the DSMB. Thus, arm 5 recruitment might start after arms 6 and 7, which may require an increase in the control arm sample size to ensure controls are recruited concomitantly.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacy and Safety Evaluation of Two to Four Months of Treatment With the Combination Regimens of DBOS and PBOS in Adults With Pulmonary Tuberculosis
NCT05971602
Platform Assessing Regimens and Durations In a Global Multisite Consortium for TB
NCT06114628
A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination With Ethionamide
NCT06748937
Phase 2 Trial Assessing TBAJ876 or Bedaquiline, with Pretomanid and Linezolid in Adults with Drug-sensitive Pulmonary Tuberculosis
NCT06058299
Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis
NCT00728507
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
A total of up to 390 (270 for stage 1 and 2, and 120 for stage 3, respectively) adult (≥ 18 years of age) participants will be enrolled.
In case of a high number of dropouts or non-evaluable participants, it may be necessary to recruit more participants into the study.
Also, if the stage 2 starts later than stage 1, it may be necessary to increase the number of control arm participants to achieve a 1:1 ratio of concomitantly recruited control and arm 4 participants until the recruitment for arm 4 is completed (see sample size considerations).
Stage 3 will start after stages 1 and 2 complete recruitment.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
In stage 1, participants will be randomly allocated to the control or one of the 2 rifampicin-containing experimental regimens in the ratio 1:1:1. In stage 2, the experimental arm 4 containing BTZ-043 will be added. The allocation ratio will be changed to co-enrol the remaining participants in arms 1- 3 simultaneously with arm 4 with an allocation ratio of 1:1:1:2. When arms 1-2 are fully enrolled and arm 4 is not, further participants will be randomized 1:1 to control and experimental arm 4. Not all countries will participate in stage 2.
In stage 3, participants will be allocated in parallel to control arm treatment (now designated arm 7) or the experimental arms 5 and 6, favouring arm 5, 2:1:1 over arms 6 and control. This stage will start after completion of recruitment in the stages 1 and 2.
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm 1 (Stage 1)
Rifampicin 2100mg, isoniazid 300mg, pyrazinamide 1600mg moxifloxacin 600mg; given once daily for 17 weeks (R2100HZM600)
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Moxifloxacin
Moxifloxacin will be dosed at 600 mg orally once daily in arms 1-2.
Arm 2 (Stage 1)
Rifampicin 2100mg, isoniazid 300mg, pyrazinamide 2000mg/2400mg, moxifloxacin 600mg; given once daily for 12 weeks (R2100HZoptM600)
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Moxifloxacin
Moxifloxacin will be dosed at 600 mg orally once daily in arms 1-2.
Arm 3
Stage 1: control arm (2HRZE-4RH) Stage 2: continuation of control-arm from STAGE 1 (2HRZE-4RH)
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Ethambutol (E)
Ethambutol 20mg/Kg OD in arm 3, 5 and 7
Arm 4 (Stage 2)
Rifampicin, Isoniazid, and Pyrazinamide in weight-banded standard dosages with BTZ-043 1,000mg; given once daily for 17 weeks (RHZT), then rifampicin and isoniazid in weight-banded dosages; given once daily for 9 weeks (RH)
BTZ-043
BTZ-043 1000mg once daily in arms 4 and 6.
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Arm 5 (Stage 3)
Alpibectir (GSK3729098) 45mg, ethionamide 500mg (A/Eto) with possibility of lower alpibectir and Eto doses based on emerging clinical data, from the ENABLE study \[ Clinical Trials gov NCT06748937\] and non-clinical data and endorsed by the GSK Global safety board, rifampicin, pyrazinamide and ethambutol at standard doses given once daily for 8 weeks, continued with RIF and INH at standard doses for 18 weeks.
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Alpibectir (GSK3729098)
Alpibectir 45 mg OD plus Ethionamide 500 mg OD combined with rifampicin pyrazinamide and ethambutol at standard weight-banded doses in arm 5.
Ethambutol (E)
Ethambutol 20mg/Kg OD in arm 3, 5 and 7
Ethionamide
Ethionamide 500mg OD in arm 5.
Arm 6 (Stage 3)
Pretomanid 200mg, ganfeborole (GSK3036656) 20mg, BTZ-043 1000mg and delpazolid (LCB01-0371) 1200mg; given once daily for 26 weeks
BTZ-043
BTZ-043 1000mg once daily in arms 4 and 6.
Ganfeborole (GSK3036656)
Ganfeborole 20 mg OD in arm 6
Delpazolid (LCB01-0371)
Delpazolid 1200mg OD in arm 6
Pretomanid (Pa)
Pretomanid 20mg OD in arm 6.
Arm 7 (Stage 3)
Parallel control arm (2HRZE-4RH)
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Ethambutol (E)
Ethambutol 20mg/Kg OD in arm 3, 5 and 7
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
BTZ-043
BTZ-043 1000mg once daily in arms 4 and 6.
Rifampicin
Rifampicin will be dosed in a fixed high-dose (2100 mg for arms 1 and 2) or a weight-banded regular dose (10 mg/kg) in arm 3, 5 and 7.
Isoniazid
Isoniazid will be dosed at fixed dose of 300mg in arms 1 and 2, and regular dose of 5 mg/kg in arm 3 and 7.
Pyrazinamide
Pyrazinamide will be dosed in a fixed regular dose in arm 1 (1600 mg), a weight banded high dose in arm 2 (2000/2400 mg) or a weight-banded regular dose (25 mg/kg) in arm 3, 5 and 7.
Moxifloxacin
Moxifloxacin will be dosed at 600 mg orally once daily in arms 1-2.
Alpibectir (GSK3729098)
Alpibectir 45 mg OD plus Ethionamide 500 mg OD combined with rifampicin pyrazinamide and ethambutol at standard weight-banded doses in arm 5.
Ganfeborole (GSK3036656)
Ganfeborole 20 mg OD in arm 6
Delpazolid (LCB01-0371)
Delpazolid 1200mg OD in arm 6
Pretomanid (Pa)
Pretomanid 20mg OD in arm 6.
Ethambutol (E)
Ethambutol 20mg/Kg OD in arm 3, 5 and 7
Ethionamide
Ethionamide 500mg OD in arm 5.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Male or female, aged between 18 and 65 years, inclusive.
3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
4. Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTB complex and rapid molecular tests result confirming susceptibility to RIF and INH such as GeneXpert and/or HAIN MTBDR plus. Participants who had a previous history of TB may be enrolled in this trial, if they:
* had a good treatment response in the opinion of the investigator; i.e. TB symptoms improved sufficiently or resolved suggesting a cure of the past episode; AND
* no persistent microbiological positivity is seen (in case microbiological results are available); AND - their treatment course was completed AND
* the last dose of treatment was more than 3 months ago.
5. A chest X-ray (no older than 2 weeks) which shows abnormalities that, in the opinion of the Investigator, are consistent with TB.
6. Sputum positive on microscopy from concentrated sputum for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale) AND/OR positive GeneXpert MTB/RIF Ultra® semi-quantitative result "medium" or "high" on at least one sputum sample.
7. The participant understands the interaction between the study drugs and certain foods and is willing to forgo the consumption of those foods for the period of study medication.
8. The participant is not of child-bearing potential or is willing to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
1. Non-childbearing potential:
i. Female participant/sexual partner of male participant: Bilateral oophorectomy, and/or hysterectomy or bilateral tubal ligation more than 12 months ago and/or has been postmenopausal with a history of no menses for at least 12 consecutive months and confirmed by a FSH test.
ii. Male participant/sexual partner of female participant: Vasectomised or has had a bilateral orchidectomy minimally three months prior to screening iii. Male participants having a pregnant female partner or a male sexual partner: At least one barrier method has to be used in this case.
b. Effective contraception methods: i. Female participants: Two methods, including methods that the participant's sexual partner(s) use. At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of experimental treatment. For stage 3, female participants of child-bearing potential must have used contraception if any sexual intercourse has occurred after last menses or within the last 3 weeks (whichever is later) before participation, and agree to use non-user dependent contraception: depo-provera injection\* or an intrauterine device additional to one barrier method.
\*Including a back-up method of contraception for at least 7 days to prevent unintended pregnancy if injection has been administered within the first 5 days of their menstrual cycle. Otherwise, a back-up barrier method of contraception is required for one month to prevent unintended pregnancy.
ii. Male participants: Two methods, including methods that the participant's female sexual partner(s) use. At least one must be a barrier method. Effective contraception must be ensured for at least 12 weeks after the last dose of experimental treatment.
Exclusion Criteria
1. Circumstances that raise doubt about free, unconstrained consent to study participation (e.g., person in detention or person with mental disability)
2. Poor general condition where delay in treatment cannot be tolerated or death within four months is likely.
3. Circumstances (in the opinion of the investigator) that raise doubt about ability to complete the follow-up during the study period.
4. The participant is pregnant or breast-feeding or planning to become pregnant in the study period.
5. The participant is infected with HIV with a CD4 count \<220 cells/mm3. If \>220 cells/mm3, participants will be included only if any of the following is applicable:
• The participant is antiretroviral (ARV) naïve and able to postpone commencing HIV treatment for 2 months after the trial has started and then restrict regimens to those mentioned in section on ARVs or
• The participant is ARV experienced (has been on ARV´s a minimum of 5 months), AND: ARV treatment is compliant to, or can be modified as described in the section on Antiretroviral Therapy
6. The participant has a known intolerance to any of the study drugs or concomitant disorders or conditions for which study drugs or standard TB treatment are contraindicated.
7. The participant has a history of, or current evidence of clinically relevant cardiovascular metabolic, gastrointestinal, neurological, hepato-biliary, renal, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially:
a. Neuropathy, or significant psychiatric disorder like depression or schizophrenia; especially if treatment for those has ever been required or is anticipated to be required b. Evidence of clinically significant extra-pulmonary TB (e.g. miliary TB, TB meningitis, but not limited lymph node involvement) c. Serious lung conditions other than TB, or significant respiratory impairment in the discretion of the investigator d. Uncontrolled diabetes mellitus or diabetes mellitus receiving/requiring treatment with metformin or sulfonylureas e. Cardiovascular disease such as myocardial infarction, heart failure, coronary heart disease, arrhythmia, tachyarrhythmia, or pulmonary hypertension f. Uncontrolled arterial hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure of ≥95 mmHg on two occasions during screening. An attempt at antihypertensive treatment during the screening period is permitted).
g. Long QT syndrome or family history of long QT syndrome or family history of sudden death of unknown or cardiac-related cause h. Alcohol, regular opiate, or other drug abuse that is sufficient to significantly compromise the safety or cooperation of the participant, that includes substances prohibited by the protocol or has led to significant organ damage at the discretion of the investigator; AND/OR any abuse of methamphetamine.
i. History of optic neuropathy j. Vitiligo
8. Any of the following laboratory findings at screening:
a. Serum amino aspartate transferase (AST) and/or alanine aminotransferase (ALT) \>3x the upper limit of normal (ULN), b. Serum alkaline phosphatase or y-glutamyl transferase \> 2.5x the ULN, c. Serum total bilirubin level \>1.5x the ULN d. Estimated creatinine clearance -eCrCl (using the CKD-EPI 2021 creatinine formula):
\- Stage 1: Lower than 30 ml/min)
\- Stage 2: Lower than 30ml/min or lower than 60 ml/min in participants living with HIV
\- Stage 3: Lower than 80ml/min e. Proteins in urine dipstick \>=2+ f. Haemoglobin level \<7.0 g/dl g. Platelet count \<50,000/mm3, h. Serum potassium below 3 mmol/l, persisting after correction.
9. ECG findings in the screening ECG: (one or more):
1. QTcF of \>450 milliseconds
2. Atrioventricular (AV) block with PR interval \> 200 milliseconds
3. QRS complex \> 120 milliseconds
4. Any other changes in the ECG that are clinically relevant as per discretion of the investigator
10. Restricted medication:
1. Treatment with any other investigational drug within 2 month prior to enrolment or enrolment into other clinical (intervention) trials during participation.
2. Previous anti-TB treatment with drugs active against MTB within the last 3 months prior to screening.
3. Unable or unwilling to abide by the requirements regarding restricted medication or have taken restricted medication. Restricted medication includes the following drug classes, with relevant timing of intake, and possible exceptions. Exceptions may be permissible after discussion with the sponsor medical expert.
18 Years
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Radboud University Medical Center
OTHER
University of California, San Francisco
OTHER
University College, London
OTHER
GlaxoSmithKline
INDUSTRY
LigaChem Biosciences, Inc.
INDUSTRY
Michael Hoelscher
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Michael Hoelscher
Prof. Dr.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Michael Hoelscher, Prof Dr.
Role: STUDY_DIRECTOR
LMU University Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Centre de Recherches Médicales de Lambaréné (CERMEL)
Lambaréné, , Gabon
Kamuzu College of Health Sciences (formerly College of Medicine)
Blantyre, , Malawi
Instituto Nacional de Saúde (INS)
Maputo, , Mozambique
Isango Lethemba TB Research Unit. Clinical HIV Research Unit (CHRU), Wits Health Consortium.
Port Elizabeth, Eastern Cape, South Africa
TASK Applied Sciences Clinical Research Centre
Cape Town, , South Africa
University of Cape Town Lung Institute
Cape Town, , South Africa
National Institute for Medical Research (NIMR-MMRC)
Mbeya, Mbeya, Tanzania
Ifakara Health Institute (IHI)
Bagamoyo, , Tanzania
Kilimanjaro Clinical Research Institute (KCRI)
Moshi, , Tanzania
Makerere University Lung Institute Limited
Kampala, , Uganda
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Marriott Nliwasa, Dr
Role: primary
Role: backup
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PanACEA - STEP2C -01
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.