Tuberculosis, PulmonaryPhase 2DECISIONNCT05926466
BTZ-043 Dose Evaluation in Combination and Selection
A Phase 2 study testing BTZ-043, Bedaquiline and Delamanid in people with Tuberculosis, Pulmonary and Other Specified Pulmonary Tuberculosis, run by Michael Hoelscher at 4 sites in 2 countries.
Trial summary
This is a phase 2B, open label study, that will compare the safety and efficacy of three experimental regimens consisting of bedaquiline and delamanid in combination with different doses of BTZ-043, a novel antibiotic, in adult participants with newly diagnosed, drug-sensitive pulmonary tuberculosis. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Tuberculosis, Pulmonary, Other Specified Pulmonary Tuberculosis
- What is being tested?
- BTZ-043, Bedaquiline and Delamanid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 21 Sep 2023to 27 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Provide written, informed consent prior to all trial-related procedures, including HIV testing.
- Male or female, aged 18 up to (and including) 64 years.
- Body weight (in light clothing and with no shoes) within the range of 30 to 100kg and body mass index within the range of 15 to 40kg/m2.
- Newly diagnosed, previously untreated current episode of drug-susceptible pulmonary TB (presence of MTB complex with rapid molecular test result confirming susceptibility to rifampicin and isoniazid such as "GeneXpert" and/or "HAIN MTBDR plus").
- ≥ 1 sputum sample from concentrated spot sputum positive in GeneXpert MTB/RIF Ultra®, with semi-quantitative result at least "medium" or higher.
- FEMALE PARTICIPANTS: Inability to conceive AND/OR inability of partner(s) to father children OR consent to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
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- Non-childbearing potential: i) 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 as per medical history.
- Sexual partner(s) of female participant: vasectomy OR bilateral orchidectomy at least three months prior to screening as per medical history.
- Effective contraception methods: i) Two methods, including methods used by patient's sexual partner(s). At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of BTZ-043.
- MALE PARTICIPANTS: Inability to father children AND/OR inability of partner(s) to conceive, OR consent to use effective methods of contraception when engaging in heterosexual intercourse, as defined below:
- Non-childbearing potential: i) Sexual partner(s) 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 as per medical history.
- Vasectomy OR bilateral orchidectomy at least three months prior to screening as per medical history.
- Female pregnant sexual partner of a male participant: agree to use at least one barrier method.
- Male sexual partner of male participant: agree to use at least one barrier method for at least until 12 weeks after the last dose of BTZ-043 for protection of the partner.
- Effective contraception methods: ii) Two methods, including methods used by patient's female sexual partner(s). At least one must be a barrier method. Effective contraception must be ensured for at least 16 weeks after the last dose of BTZ-043
Who cannot join
- Circumstances that raise doubt about free, unconstrained consent to study participation (e.g. in a prisoner or person suffering from an intellectual disability).
- Poor general condition, where delay in treatment cannot be tolerated, or death within three months is likely, as assessed by the investigator.
- Poor social condition which would result in a high likelihood of not completing the trial until the final visit.
- The patient is pregnant or breast-feeding.
- The patient is HIV antibody positive (known, or on a test performed at screening), unless:
- The patient has a viral load (VL) < 200 copies/mL on a test performed at screening
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- The patient has a CD4 cell count > 200 cells/mm3 at screening
- The patient is experienced on antiretroviral therapy (ART), and is on a combination of tenofovir, lamivudine and dolutegravir (TDF/3TC/DTG) for a minimum of 6 months prior to the screening visit.
- The patient 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.
- The patient has received treatment with any other investigational drug within 1 month prior to enrolment, or is planning to be enrolled into other clinical (intervention) trials during participation.
- The patient has a history of or current evidence of clinically relevant cardiovascular, metabolic, gastrointestinal, neurological, ophthalmological, 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:
- Clinically significant evidence of severe or extra-thoracic TB (e.g., miliary TB, TB meningitis, excluding limited lymph node involvement)
- Serious lung conditions other than TB or significant respiratory impairment in the discretion of the investigator
- Peripheral neuropathy (as evaluated by the Brief Peripheral Neuropathy Score).
- Significant psychiatric disorder like depression or schizophrenia; especially if treatment for those has ever been required in the last five years or is anticipated to be required.
- An established diagnosis of diabetes mellitus.
- Cardiovascular disease, such as myocardial infarction, heart failure, coronary heartdisease, arrhythmia, tachyarrhythmia, or pulmonary hypertension.
- Current (as measured on two occasions during screening) or history of hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg) on two occasions. Controlled hypertension is permitted if the patients receive only the allowed anti-hypertensives.
- Long QT syndrome or family history of long QT syndrome or sudden death of unknown or cardiac-related cause.
- Alcohol or other drug abuse, that is sufficient to significantly compromise the safety or cooperation of the patient, includes substances prohibited by the protocol, or has led to significant organ damage, at the discretion of the investigator. An isolated positive test for cannabinoids does not fulfil this exclusion criterion.
- Chronic kidney disease (CKD) or any other history of renal impairment.
- Any of the following laboratory findings at screening:
- serum amino aspartate transferase (AST) and/or alanine aminotransferase (ALT) activity >3x the ULN
- serum alkaline phosphatase (ALP) >3x the ULN
- serum total bilirubin level >1.5 times the ULN
- estimated creatinine clearance (eCrCl) < 60 mls/min (calculated using the Cockcroft and Gault formula
- haemoglobin level <8.0 g/dL
- platelet count <50,000/mm3
- albumin < 2.8 g/dl
- serum potassium <3.5 mmol/L (not excluded if subsequently corrected)
- serum magnesium < 0.5mmol/L (not excluded if subsequently corrected)
- Any of the following ECG findings at screening:
- QTcF of > 450 milliseconds (ms)
- Atrioventricular (AV) block with PR interval > 200 ms
- QRS complex > 120 ms
- any other changes in the ECG that are clinically relevant as per discretion of the investigator
- Any of the following regarding concomitant medications at screening:
- Previous treatment with first- and second-line anti-TB drugs within the last 3 months prior to screening.
- Treatment with any other investigational drug (including vaccines) within 1 month prior to enrolment or enrolment into other clinical (interventional) trials during participation.
- Unable or unwilling to only take the allowed concomitant medications for this studyand ensuring an appropriate washout period
- Unable or unwilling to abide to the dietary restrictions required in this study
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
South Africa2 sites
TASK Applied Sciences Clinical Research Centre
Cape Town, 7500
TASK Applied Science Eden
George, 6529
Tanzania2 sites
National Institute for Medical Research (NIMR-MMRC)
Mbeya
National Institute for Medical Research (NIMR-Mwanza),
Mwanza
About this study
Official title: A Phase IIb, Open-Label, Randomized Controlled Dose Ranging Multi-Center Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Exposure-Response Relationship of Different Doses of BTZ-043 in Combination With Bedaquiline and Delamanid in Adult Subjects With Newly Diagnosed, Uncomplicated, Drug-sensitive Pulmonary Tuberculosis
This is a phase 2B, open label study, that will compare the safety and efficacy of three experimental regimens consisting of bedaquiline and delamanid in combination with different doses of BTZ-043, a novel antibiotic, in adult participants with newly diagnosed, drug-sensitive pulmonary tuberculosis. Participants will be assigned to receive either one of the three BTZ-043-containing regimens or a comparator regimen consisting of bedaquiline, delamanid and moxifloxacin. The objective is to find the optimal dose of BTZ-043 with the highest efficacy and safety to be used in subsequent studies.
Read the detailed description
This open label, phase 2B, randomized controlled study will evaluate three experimental arms containing different doses of BTZ-043 in combination with bedaquiline and delamanid, in adult subjects with newly diagnosed, drug-sensitive pulmonary tuberculosis, in comparison with bedaquiline, delamanid and moxifloxacin, administered over 16 weeks. A total of 90 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.
The participants will be randomly allocated to one of the three BTZ-containing experimental regimens or the moxifloxacin-containing comparator regimen:
Arm 1: bedaquiline, delamanid, BTZ-043 500 mg (BDT500) Arm 2: bedaquiline, delamanid, BTZ-043 1000 mg (BDT1000) Arm 3: bedaquiline, delamanid, BTZ-043 1500 mg (BDT1500) Arm 4: bedaquiline, delamanid, moxifloxacin (BDM) In all arms, bedaquiline will be dosed at 400 mg once daily for 2 weeks, followed by 100 mg once daily for 14 weeks and delamanid will be dosed at 300 mg once daily for 16 weeks. Moxifloxacin will be dosed at 400 mg once daily in the comparator arm. After completion of 16 weeks of treatment, all participants will receive 8 weeks of continuation therapy with Rifampicin and Isoniazid.
- Being tested
- BTZ-043, Bedaquiline, Delamanid, Moxifloxacin
- Keywords
- Tuberculosis, BTZ-043, Bedaquiline, Delamanid, Moxifloxacin, Safety, Tolerability, Pharmacokinetics (PK), Benzothiazinones, Pulmonary Tuberculosis, Dose-finding, Antitubercular agents
- Medical subject headings
- Tuberculosis, Pulmonary, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BTZ-043Drug
BTZ-043 belongs to the chemical class of benzothiazinones, and is a promising antibiotic for the treatment of Tuberculosis. Its mechanism of action is based on the covalent inhibition of the enzyme decaprenylphosphoryl-ß-D-ribose-2'-epimerase (DprE1), which is essential for the cell wall assembly of mycobacteria. . Formation of the covalent adduct between BTZ-043 and DprE1 results in inhibition of cell wall biosynthesis and loss of viability of Mycobacteria Tuberculosis. BTZ-043 has been evaluated in three clinical studies: a phase Ia, First Time in Human study (FTIH), a two-stage phase Ib multiple ascending dose (MAD) and phase IIa monotherapy early bactericidal activity (EBA) study, and a human ADME (Absorption/Distribution/Metabolism/Excretion) study.
BedaquilineDrug
Also called SIRTURO®
Bedaquiline, is a diarylquinoline compound with a novel mechanism of action against MTB, the inhibition of mycobacterial adenosine triphosphate (ATP) synthase. On the 28th of December 2012, the Food and Drug Administration (FDA) granted accelerated approval to SIRTURO® (bedaquiline) tablets as a part of combination therapy in adults with MDR-TB. It is the first to be introduced specifically for the treatment of MDR-TB in combination with other drugs.
DelamanidDrug
Also called OPC-67683, Deltyba
Delamanid is a nitro-dihydro-imidazooxazole derivative that inhibits the synthesis of mycolic acids, a crucial component of the cell wall of MTB. Delamanid has received regulatory approvals in several countries and is currently recommended by WHO for for use in longer MDR- or RR-TB regimens in line with WHO recommendations.
MoxifloxacinDrug
Also called Lonxave
Moxifloxacin belongs to the group of fluoroquinolones (FQ). FQs are a mainstay of MDR-TB treatment, and Moxifloxacin is considered the most potent drug in second line MDR-TB therapy, recently reviewed by WHO, with only moderate pre-existing resistance in the community.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | Drug: Moxifloxacin Moxifloxacin will be dosed at the licensed dose of 400 mg orally once daily for 16 weeks Drug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Receives: Drug: Bedaquiline; Drug: Delamanid; Drug: Moxifloxacin |
| Arm 2 | Experimental | Drug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 500 mg orally once daily for 16 weeks Receives: Drug: BTZ-043; Drug: Bedaquiline; Drug: Delamanid |
| Arm 3 | Experimental | Drug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 1000 mg orally once daily for 16 weeks Receives: Drug: BTZ-043; Drug: Bedaquiline; Drug: Delamanid |
| Arm 4 | Experimental | Drug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 1500 mg orally once daily for 16 weeks Receives: Drug: BTZ-043; Drug: Bedaquiline; Drug: Delamanid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to positivity in BD MGIT liquid culture
To evaluate which of the BTZ-043 containing experimental arms is superior, the change in mycobacterial load over time on treatment as quantified by time to positivity in BD MGIT 960® (Mycobacterium Growth Tube Indicator) liquid culture described by non-linear mixed-effects methodology
Measured: Day 01- Day 112
Secondary outcomes (15)
Time to stable culture conversion to negative in liquid media
The time on treatment required until a participant achieves the first of two successive visits with negative cultures without an intervening positive culture
Measured: Day 01- Day 112
Proportion of participants converting to negative sputum culture in liquid media
Proportion of participants converting to negative sputum culture in liquid media defined as two consecutive negative cultures without an intervening positive culture) at each time point during treatment
Measured: Day 01- Day 112
Frequency of all adverse events (serious and non-serious)
To assess the frequency, severity, and type of adverse events (AEs), and AE related treatment discontinuations.
Measured: Day 01- Day 168
Frequency of adverse events of Grade 3 severity (severe) or higher
Severity of AEs will be classified following the U.S. National Institutes of Health Common Terminology Criteria for Adverse Events 5.0 (CTCAE). The minimum grade is 1 (Mild) and the maximum grade is 5 (Death related to AE).
Higher scores mean a worse outcome
Measured: Day 01- Day 168
Frequency of adverse events possibly, probably or definitely related to study drug
To assess the frequency, severity, and type of adverse events (AEs), and AE related treatment discontinuations.
Measured: Day 01- Day 168
Frequency of treatment discontinuations or interruptions related to adverse events/serious adverse event
To assess the frequency, severity, and type of adverse events (AEs), and AE related treatment discontinuations.
Measured: Day 01- Day 168
Changes in ECG intervals of PR, RR, QRS, QT, Fridericia-corrected QT [QTcF]
- Proportion of participants with QTcF > 500ms in ECGs on treatment. • Proportion of participants who have a QTcF prolongation of grade 3 or higher
Measured: Day 01- Day 168
Area under the plasma concentration curve from dosing to the end of the dosing interval (AUC 0-24)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
The observed maximum concentration (Cmax)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
Time to reach Cmax (Tmax)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
Minimum observed plasma concentration 24 hours following the last dose (Cmin)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
Apparent oral clearance (Cl/F)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
Terminal half-life (t 1/2)
The pharmacokinetics parameters will be assessed for BTZ-043, bedaquiline and delamanid, and their major metabolites (Arm 2-4), in all participants. Extensive sampling will be done for BTZ-043 at the WK04 visit (Day 28 ± 2 Days) and sparse PK sampling for bedaquiline and delamanid on WK04 (Day 28 ± 2 Days) and WK08 visits (Day 56 ± 2 Days)
Measured: Day 28, Day 56
Identification of M. tuberculosis complex and Isoniazid (INH) resistance by PCR (GeneXpert Ultra MTB/RIF®/ GeneXpert XDR/HAIN MTBDRplus or similar)
Cultures grown from the screening period, and the last sputum sample with mycobacteriological growth will be assessed. This test is qualitative, therefore the result will be: Detected, not detected or indeterminate
Measured: Day 01-Day 112
Minimum inhibitory concentrations (MIC) of study drugs the patient was receiving
Cultures grown from the screening period, and the last sputum sample with mycobacteriological growth will be assessed.
Measured: Day 01- Day 112
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start21 Sep 2023
- Primary completion27 Dec 2024
- Study completion27 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberculosis, PulmonaryStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will compare the efficacy, safety of 3 experimental regimens with a comparator regimen administered over 16 weeks, in participants with newly diagnosed, drug sensitive pulmonary tuberculosis.
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Hoelscher
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, University of California, San Francisco, University College, London
- Responsible party
- Sponsor-investigator, Michael Hoelscher, Ludwig-Maximilians - University of Munich
- Investigators
- Michael Hoelscher, Prof Dr, Study director, LMU University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05926466
- Sponsor's protocol ID
- LMU-IMPH-BTZ-043-04
- Other IDs
- UNITE4TB-02
- Acronym
- DECISION
- Status last verified
- Oct 2026
- First submitted
- 22 Jun 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data collected for the study include de-identified individual participant data and a data dictionary defining each field in the set. Which will be made available via C-path
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Open-Label, Randomized Controlled Dose Ranging Multi-Center Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Exposure-Response Relationship of Different Doses of BTZ-043 in Combination With Bedaquiline and Delamanid in Adult Subjects With Newly Diagnosed, Uncomplicated, Drug-sensitive Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT05926466
- Acronym / sponsor ID
- DECISION / LMU-IMPH-BTZ-043-04
- Keywords
- Tuberculosis, BTZ-043, Bedaquiline, Delamanid, Moxifloxacin, Safety, Tolerability, Pharmacokinetics (PK)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Michael HoelscherUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, University of California, San Francisco, University College, London
- Study start
- 21 Sep 2023 (actual)
- Primary completion
- 27 Dec 2024 (actual)
- Study completion
- 27 Dec 2024 (actual)
- First posted
- 3 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2B, open label study, that will compare the safety and efficacy of three experimental regimens consisting of bedaquiline and delamanid in combination with different doses of BTZ-043, a novel antibiotic, in adult participants with newly diagnosed, drug-sensitive pulmonary tuberculosis. Participants will be assigned to receive either one of the three BTZ-043-containing regimens or a comparator regimen consisting of bedaquiline, delamanid and moxifloxacin. The objective is to find the optimal dose of BTZ-043 with the highest efficacy and safety to be used in subsequent studies.
Detailed description
This open label, phase 2B, randomized controlled study will evaluate three experimental arms containing different doses of BTZ-043 in combination with bedaquiline and delamanid, in adult subjects with newly diagnosed, drug-sensitive pulmonary tuberculosis, in comparison with bedaquiline, delamanid and moxifloxacin, administered over 16 weeks. A total of 90 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.
The participants will be randomly allocated to one of the three BTZ-containing experimental regimens or the moxifloxacin-containing comparator regimen:
Arm 1: bedaquiline, delamanid, BTZ-043 500 mg (BDT500) Arm 2: bedaquiline, delamanid, BTZ-043 1000 mg (BDT1000) Arm 3: bedaquiline, delamanid, BTZ-043 1500 mg (BDT1500) Arm 4: bedaquiline, delamanid, moxifloxacin (BDM) In all arms, bedaquiline will be dosed at 400 mg once daily for 2 weeks, followed by 100 mg once daily for 14 weeks and delamanid will be dosed at 300 mg once daily for 16 weeks. Moxifloxacin will be dosed at 400 mg once daily in the comparator arm. After completion of 16 weeks of treatment, all participants will receive 8 weeks of continuation therapy with Rifampicin and Isoniazid.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The study will compare the efficacy, safety of 3 experimental regimens with a comparator regimen administered over 16 weeks, in participants with newly diagnosed, drug sensitive pulmonary tuberculosis.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Drug: Bedaquiline, Drug: Delamanid, Drug: MoxifloxacinDrug: Moxifloxacin Moxifloxacin will be dosed at the licensed dose of 400 mg orally once daily for 16 weeks Drug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks |
| Arm 2 | Experimental | Drug: BTZ-043, Drug: Bedaquiline, Drug: DelamanidDrug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 500 mg orally once daily for 16 weeks |
| Arm 3 | Experimental | Drug: BTZ-043, Drug: Bedaquiline, Drug: DelamanidDrug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 1000 mg orally once daily for 16 weeks |
| Arm 4 | Experimental | Drug: BTZ-043, Drug: Bedaquiline, Drug: DelamanidDrug: Bedaquiline Bedaquiline will be dosed at 400 mg orally once daily for the first 2 weeks, followed by 100 mg orally once daily for 14 weeks Drug: Delamanid Delamanid will be dosed at 300 mg orally once daily for 16 weeks Drug: BTZ-043 BTZ-043 will be dosed at 1500 mg orally once daily for 16 weeks |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Provide written, informed consent prior to all trial-related procedures, including HIV testing.
- Male or female, aged 18 up to (and including) 64 years.
- Body weight (in light clothing and with no shoes) within the range of 30 to 100kg and body mass index within the range of 15 to 40kg/m2.
- Newly diagnosed, previously untreated current episode of drug-susceptible pulmonary TB (presence of MTB complex with rapid molecular test result confirming susceptibility to rifampicin and isoniazid such as "GeneXpert" and/or "HAIN MTBDR plus").
- ≥ 1 sputum sample from concentrated spot sputum positive in GeneXpert MTB/RIF Ultra®, with semi-quantitative result at least "medium" or higher.
Key exclusion criteria (41 listed)
- Circumstances that raise doubt about free, unconstrained consent to study participation (e.g. in a prisoner or person suffering from an intellectual disability).
- Poor general condition, where delay in treatment cannot be tolerated, or death within three months is likely, as assessed by the investigator.
- Poor social condition which would result in a high likelihood of not completing the trial until the final visit.
- The patient is pregnant or breast-feeding.
- The patient is HIV antibody positive (known, or on a test performed at screening), unless:
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 |
|---|---|---|
| BTZ-043BTZ-043 belongs to the chemical class of benzothiazinones, and is a promising antibiotic for the treatment of Tuberculosis. Its mechanism of action is based on the covalent inhibition of the enzyme decaprenylphosphoryl-ß-D-ribose-2'-epimerase (DprE1), which is essential for the cell wall assembly of mycobacteria. . Formation of the covalent adduct between BTZ-043 and DprE1 results in inhibition of cell wall biosynthesis and loss of viability of Mycobacteria Tuberculosis. BTZ-043 has been evaluated in three clinical studies: a phase Ia, First Time in Human study (FTIH), a two-stage phase Ib multiple ascending dose (MAD) and phase IIa monotherapy early bactericidal activity (EBA) study, and a human ADME (Absorption/Distribution/Metabolism/Excretion) study. | Drug | Arm 2, Arm 3, Arm 4 |
| BedaquilineAlso: SIRTURO®Bedaquiline, is a diarylquinoline compound with a novel mechanism of action against MTB, the inhibition of mycobacterial adenosine triphosphate (ATP) synthase. On the 28th of December 2012, the Food and Drug Administration (FDA) granted accelerated approval to SIRTURO® (bedaquiline) tablets as a part of combination therapy in adults with MDR-TB. It is the first to be introduced specifically for the treatment of MDR-TB in combination with other drugs. | Drug | Arm 1, Arm 2, Arm 3, Arm 4 |
| DelamanidAlso: OPC-67683, DeltybaDelamanid is a nitro-dihydro-imidazooxazole derivative that inhibits the synthesis of mycolic acids, a crucial component of the cell wall of MTB. Delamanid has received regulatory approvals in several countries and is currently recommended by WHO for for use in longer MDR- or RR-TB regimens in line with WHO recommendations. | Drug | Arm 1, Arm 2, Arm 3, Arm 4 |
| MoxifloxacinAlso: LonxaveMoxifloxacin belongs to the group of fluoroquinolones (FQ). FQs are a mainstay of MDR-TB treatment, and Moxifloxacin is considered the most potent drug in second line MDR-TB therapy, recently reviewed by WHO, with only moderate pre-existing resistance in the community. | Drug | Arm 1 |
Primary outcome
Time to positivity in BD MGIT liquid culture
Time frame: Day 01- Day 112
To evaluate which of the BTZ-043 containing experimental arms is superior, the change in mycobacterial load over time on treatment as quantified by time to positivity in BD MGIT 960® (Mycobacterium Growth Tube Indicator) liquid culture described by non-linear mixed-effects methodology
15 secondary outcomes
Time to stable culture conversion to negative in liquid media
Time frame: Day 01- Day 112
Proportion of participants converting to negative sputum culture in liquid media
Time frame: Day 01- Day 112
Frequency of all adverse events (serious and non-serious)
Time frame: Day 01- Day 168
Frequency of adverse events of Grade 3 severity (severe) or higher
Time frame: Day 01- Day 168
Frequency of adverse events possibly, probably or definitely related to study drug
Time frame: Day 01- Day 168
Frequency of treatment discontinuations or interruptions related to adverse events/serious adverse event
Time frame: Day 01- Day 168
Changes in ECG intervals of PR, RR, QRS, QT, Fridericia-corrected QT [QTcF]
Time frame: Day 01- Day 168
Area under the plasma concentration curve from dosing to the end of the dosing interval (AUC 0-24)
Time frame: Day 28, Day 56
The observed maximum concentration (Cmax)
Time frame: Day 28, Day 56
Time to reach Cmax (Tmax)
Time frame: Day 28, Day 56
Minimum observed plasma concentration 24 hours following the last dose (Cmin)
Time frame: Day 28, Day 56
Apparent oral clearance (Cl/F)
Time frame: Day 28, Day 56
Terminal half-life (t 1/2)
Time frame: Day 28, Day 56
Identification of M. tuberculosis complex and Isoniazid (INH) resistance by PCR (GeneXpert Ultra MTB/RIF®/ GeneXpert XDR/HAIN MTBDRplus or similar)
Time frame: Day 01-Day 112
Minimum inhibitory concentrations (MIC) of study drugs the patient was receiving
Time frame: Day 01- Day 112
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: Yes. Data collected for the study include de-identified individual participant data and a data dictionary defining each field in the set. Which will be made available via C-path
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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.
Michael Hoelscher, Prof Dr study director
LMU University Hospital
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BTZ-043, Bedaquiline and Delamanid in people with Tuberculosis, Pulmonary and Other Specified Pulmonary Tuberculosis, run by Michael Hoelscher at 4 sites in 2 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 15 inclusion and 41 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 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Africa, Tanzania. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to positivity in BD MGIT liquid culture (time frame: Day 01- Day 112). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Oct 2026.