Trial Outcomes & Findings for Ultra-Short Course Bedaquiline, Clofazimine, Pyrazinamide and Delamanid Versus Standard Therapy for Drug-Susceptible Tuberculosis (NCT NCT05556746)
NCT ID: NCT05556746
Last Updated: 2026-08-05
Results Overview
Culture conversion is defined as the first of two negative sputum cultures, consecutive or not, without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs or symptoms of active tuberculosis (TB).
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
94 participants
Primary outcome timeframe
Measured through Week 8
Results posted on
2026-08-05
Participant Flow
Participants were enrolled from November 24, 2023 to April 8, 2025 at two non-US clinical research sites.
Randomization was stratified by presence of lung cavitation and HIV status
Participant milestones
| Measure |
Arm 1 BCZD
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
48
|
|
Overall Study
COMPLETED
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
38
|
41
|
Reasons for withdrawal
| Measure |
Arm 1 BCZD
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Went off study at week 60 or 72 due to funding constraints
|
18
|
18
|
|
Overall Study
Under Study Follow-up
|
15
|
22
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Arm 1 BCZD
n=46 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
Total
n=94 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.5 years
n=46 Participants
|
33 years
n=48 Participants
|
33.5 years
n=94 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=46 Participants
|
16 Participants
n=48 Participants
|
35 Participants
n=94 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=46 Participants
|
32 Participants
n=48 Participants
|
59 Participants
n=94 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Haiti
|
20 Participants
n=46 Participants
|
22 Participants
n=48 Participants
|
42 Participants
n=94 Participants
|
|
Region of Enrollment
South Africa
|
26 Participants
n=46 Participants
|
26 Participants
n=48 Participants
|
52 Participants
n=94 Participants
|
|
HIV Status
Negative
|
40 Participants
n=46 Participants
|
41 Participants
n=48 Participants
|
81 Participants
n=94 Participants
|
|
HIV Status
Positive
|
6 Participants
n=46 Participants
|
7 Participants
n=48 Participants
|
13 Participants
n=94 Participants
|
|
Cavitation per Chest X-ray for randomization stratification
Absent
|
13 Participants
n=46 Participants
|
13 Participants
n=48 Participants
|
26 Participants
n=94 Participants
|
|
Cavitation per Chest X-ray for randomization stratification
Present
|
33 Participants
n=46 Participants
|
35 Participants
n=48 Participants
|
68 Participants
n=94 Participants
|
PRIMARY outcome
Timeframe: Measured through Week 8Population: Enrolled participants who were not late exclusions. Late exclusion is defined as screening, baseline study, or Week 1 visit sputum cultures failed to grow M. tuberculosis, or resistance to RIF or INH was detected from baseline molecular or phenotypic testing results that became available after enrollment.
Culture conversion is defined as the first of two negative sputum cultures, consecutive or not, without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs or symptoms of active tuberculosis (TB).
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=47 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Median Time to Stable Liquid Culture Conversion by Week 8
|
8 weeks
Interval 1.0 to 8.0
|
6 weeks
Interval 1.0 to 8.0
|
SECONDARY outcome
Timeframe: Measured at Week 60AEs include any occurrence that is new in onset or aggravated at least one-grade from baseline. AE's are graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured at Week 60Favorable composite outcome is defined as no failure, relapse, or non-accidental death.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured at Week 12 in Arm 1 and Week 26 in Arm 2Population: All participants enrolled
Premature treatment discontinuation is defined as discontinuation other than due to violent death, natural disaster, or administrative censoring
Outcome measures
| Measure |
Arm 1 BCZD
n=46 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Proportion Who Prematurely Discontinue Treatment
|
0.130 proportion of participants
Interval 0.049 to 0.263
|
0.021 proportion of participants
Interval 0.001 to 0.111
|
SECONDARY outcome
Timeframe: Measured through Week 12Population: Enrolled participants who were not late exclusions. Late exclusion is defined as screening, baseline study, or Week 1 visit sputum cultures failed to grow M. tuberculosis, or resistance to RIF or INH was detected from baseline molecular or phenotypic testing results that became available after enrollment.
Culture conversion is defined as the first of two negative sputum cultures, consecutive or not, without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs or symptoms of active TB
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=47 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Median Time to Stable Liquid Culture Conversion by Week 12
|
8 weeks
Interval 6.0 to 10.0
|
6 weeks
Interval 4.0 to 8.0
|
SECONDARY outcome
Timeframe: Weeks 8, 12, 16, 26, 60, and 86Participants rate any change in skin color since TB treatment started on subjective 10-point numeric rating scale where 0=none, 10=worst possible change in coloration.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 8, 12, 16, 26, 60, and 86Participants rate distress from change in skin color since TB treatment started on subjective 10-point numeric rating scale where 0=none, 10=worst possible distress due to coloration.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (screening visit) and weeks 1, 2, 4, 8, 12, and 16Population: Enrolled participants who have QTcF data available at specified weeks.
The QTcF is derived from ECG readings, which the sites conducted in triplicate (three ECGs 5-10 minutes apart). The mean of all measurements (up to 3) that are readable and available are used at each of baseline (screening visit), Week 1, Week 2, Week 4, Week 8, Week 12, and Week 16.
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 1
|
24.8 milliseconds
Standard Deviation 21.2
|
5.0 milliseconds
Standard Deviation 22.1
|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 2
|
23.4 milliseconds
Standard Deviation 21.3
|
5.5 milliseconds
Standard Deviation 24.5
|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 4
|
30.3 milliseconds
Standard Deviation 20.8
|
4.0 milliseconds
Standard Deviation 25.0
|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 8
|
31.9 milliseconds
Standard Deviation 18.8
|
4.4 milliseconds
Standard Deviation 28.7
|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 12
|
26.2 milliseconds
Standard Deviation 23.6
|
7.1 milliseconds
Standard Deviation 24.8
|
|
Mean Change in QTcF From Baseline to Week 1, 2, 4, 8, 12, and 16
Week 16
|
25.7 milliseconds
Standard Deviation 20.7
|
8.8 milliseconds
Standard Deviation 21.3
|
SECONDARY outcome
Timeframe: Measured at Week 12 in Arm 1 and Week 26 in Arm 2Population: Enrolled participants who have QTcF data available at the end of treatment (week 12 in Arm 1 and Week 26 in Arm 2).
The QTcF is derived from ECG readings, which the sites conducted in triplicate (three ECGs 5-10 minutes apart). The mean of all measurements (up to 3) that are readable and available are used at baseline (screening visit) and week 12 (Arm 1). ECG was not required at week 26 per the protocol thus the week 26 data was not collected.
Outcome measures
| Measure |
Arm 1 BCZD
n=43 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Mean Change in QTcF From Baseline to End of Treatment
|
26.2 milliseconds
Standard Deviation 23.6
|
—
|
SECONDARY outcome
Timeframe: Measured through Week 16Population: Enrolled participants who have QTcF data available.
The QTcF is derived from ECG readings, which the sites conducted in triplicate (three ECGs 5-10 minutes apart). The mean of all measurements (up to 3) that are readable and available are used through week 16 in Arm 1 and Arm 2
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Occurrence of Absolute QTcF >480 ms and ≤500 ms, and >500 ms
≤480 ms
|
44 Participants
|
48 Participants
|
|
Occurrence of Absolute QTcF >480 ms and ≤500 ms, and >500 ms
>480 to ≤500 ms
|
1 Participants
|
0 Participants
|
|
Occurrence of Absolute QTcF >480 ms and ≤500 ms, and >500 ms
>500 ms
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Measured through Week 16Population: Enrolled participants who have QTcF data available
The QTcF is derived from ECG readings, which the sites conducted in triplicate (three ECGs 5-10 minutes apart). The mean of all measurements (up to 3) that are readable and available are used at baseline (screening visit) and through week 16 in Arm 1 and Arm 2
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Occurrence of QTcF Change From Baseline of >30 ms and ≤60 ms, and >60 ms
≤30 ms
|
6 Participants
|
34 Participants
|
|
Occurrence of QTcF Change From Baseline of >30 ms and ≤60 ms, and >60 ms
>30 to ≤60 ms
|
31 Participants
|
11 Participants
|
|
Occurrence of QTcF Change From Baseline of >30 ms and ≤60 ms, and >60 ms
>60 ms
|
8 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Measured through Week 86An SAE is defined as any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but based upon appropriate medical judgment may jeopardize the participant and may require intervention to prevent one of the outcomes listed in the definition above.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured at Weeks 4, 8, and 12Population: Enrolled participants who were not late exclusions and were mycobacterium tuberculosis (MTB)-positive in liquid media at the screening, study entry, or week 1 visit.
Proportion of participants who have achieved stable culture conversion, defined as two negative sputum cultures, consecutive or not, without an intervening positive culture and/or visits wherein the participant is unable to produce sputum and has no signs of active TB; occurring before or at the week 4, 8, or 12 visit, respectively.
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=47 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Proportion With Culture Conversion in Liquid Media at Weeks 4, 8 and 12
Week 12
|
0.844 proportion of participants
Interval 0.705 to 0.935
|
1.000 proportion of participants
Interval 0.925 to 1.0
|
|
Proportion With Culture Conversion in Liquid Media at Weeks 4, 8 and 12
Week 4
|
0.244 proportion of participants
Interval 0.129 to 0.395
|
0.298 proportion of participants
Interval 0.173 to 0.449
|
|
Proportion With Culture Conversion in Liquid Media at Weeks 4, 8 and 12
Week 8
|
0.667 proportion of participants
Interval 0.51 to 0.8
|
0.809 proportion of participants
Interval 0.667 to 0.909
|
SECONDARY outcome
Timeframe: Measured at Weeks 4, 8, and 12Population: Enrolled participants who were not late exclusions and were MTB-culture positive in solid media at the screening, study entry, or week 1 visit.
Proportion of participants who have achieved stable culture conversion, defined as two negative sputum cultures, consecutive or not, without an intervening positive culture and/or visits wherein the participant is unable to produce sputum and has no signs of active TB; occurring before or at the week 4, 8, or 12 visit, respectively.
Outcome measures
| Measure |
Arm 1 BCZD
n=44 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=44 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Proportion With Culture Conversion in Solid Media at Weeks 4, 8 and 12
Week 4
|
0.455 proportion of participants
Interval 0.304 to 0.612
|
0.591 proportion of participants
Interval 0.432 to 0.737
|
|
Proportion With Culture Conversion in Solid Media at Weeks 4, 8 and 12
Week 8
|
0.886 proportion of participants
Interval 0.754 to 0.962
|
0.955 proportion of participants
Interval 0.845 to 0.994
|
|
Proportion With Culture Conversion in Solid Media at Weeks 4, 8 and 12
Week 12
|
0.955 proportion of participants
Interval 0.845 to 0.994
|
1.000 proportion of participants
Interval 0.92 to 1.0
|
SECONDARY outcome
Timeframe: Measured from end of treatment (week 12 for Arm 1 and week 26 for Arm2) through Week 86For participants who had successful culture conversion through the end of study treatment, TB relapse is defined as a recurrence of TB emanating from the same strain as the participant's originally diagnosed TB, which will be determined through whole genome sequencing.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Measured through Week 86For participants in experimental group only. Minimum Inhibitory Concentration (MIC) values will be evaluated against resistance-associated variants (RAVs) for paired baseline and failure isolates. Frequencies and proportions with phenotypic and/or genotypic resistance to any drug will be reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 6, and 8Population: Enrolled participants who were not late exclusions and have liquid culture data available at specified weeks.
Time to positivity in liquid culture is defined as the days required for a sample to exhibit detectable microbial growth (positive result) in liquid media. A shorter time to positivity indicates a higher concentration of viable microorganisms in the original sample. Participants with a negative liquid culture result were imputed to have the 'best' time to positivity of 43 days (\>42 days), and participants with contaminated culture results were excluded. Sputum samples were collected at weeks 1, 2, 3, 4, 6, and 8 for culture in liquid media.
Outcome measures
| Measure |
Arm 1 BCZD
n=45 Participants
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=47 Participants
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Median Time (Days) to Positivity in Liquid Culture
Week 1
|
11 days
Interval 9.0 to 16.0
|
11 days
Interval 10.0 to 15.0
|
|
Median Time (Days) to Positivity in Liquid Culture
Week 2
|
14 days
Interval 11.0 to 16.5
|
14 days
Interval 12.0 to 28.0
|
|
Median Time (Days) to Positivity in Liquid Culture
Week 3
|
16.5 days
Interval 13.0 to 28.0
|
18 days
Interval 15.0 to 33.0
|
|
Median Time (Days) to Positivity in Liquid Culture
Week 4
|
20.5 days
Interval 14.5 to 43.0
|
24 days
Interval 17.0 to 43.0
|
|
Median Time (Days) to Positivity in Liquid Culture
Week 6
|
43 days
Interval 21.0 to 43.0
|
43 days
Interval 26.0 to 43.0
|
|
Median Time (Days) to Positivity in Liquid Culture
Week 8
|
43 days
Interval 30.0 to 43.0
|
43 days
Interval 43.0 to 43.0
|
Adverse Events
Arm 1 BCZD
Serious events: 4 serious events
Other events: 13 other events
Deaths: 2 deaths
Arm 2 RHZE
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm 1 BCZD
n=46 participants at risk
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 participants at risk
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Psychiatric disorders
Delirium
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Infections and infestations
Sepsis
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Infections and infestations
Tuberculosis
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
Other adverse events
| Measure |
Arm 1 BCZD
n=46 participants at risk
BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.
Bedaquiline (BDQ): Daily therapy for 12 weeks
Clofazimine (CFZ): Daily therapy for 12 weeks
Pyrazinamide (PZA): Daily therapy for 12 weeks
Delamanid (DLM): Daily therapy for 12 weeks
|
Arm 2 RHZE
n=48 participants at risk
RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks; given daily in fixed dose combinations at standard weight-based doses.
Rifampicin (RIF): Daily therapy for 26 weeks
Isoniazid (INH): Daily therapy for 26 weeks
Ethambutol (EMB): Daily therapy for 8 weeks
Pyrazinamide (PZA): Daily therapy for 8 weeks
|
|---|---|---|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Investigations
Alanine aminotransferase increased
|
4.3%
2/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
2.1%
1/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
2.1%
1/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Investigations
Electrocardiogram QT prolonged
|
13.0%
6/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
6.2%
3/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Investigations
Haemoglobin decreased
|
4.3%
2/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
2.1%
1/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Investigations
Neutrophil count decreased
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
4.2%
2/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
|
Blood and lymphatic system disorders
Hypochromic anaemia
|
2.2%
1/46 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
0.00%
0/48 • From study entry to study completion, up to 86 weeks.
AEs led to a change in study treatment regardless of grade, meeting the SAE definition, Grade ≥3, or Grade ≥2 AEs for Conduction abnormality/atrioventricular heart block, QTcF prolongation, Hyperpigmentation, Dry skin, Photosensitivity, Pruritus/itching, Rash, Hepatitis as defined by elevations in ALT, AST, or total bilirubin were reported. AEs of blood creatinine increased and creatinine renal clearance decreased were excluded based on the DSMB recommendation to use absolute creatinine levels.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place