This trial will assess the safety and efficacy of OPC-167832 combined with delamanid and bedaquiline in participants with drug-susceptible tuberculosis (DS-TB) administered for 17 weeks compared to rifampin, isoniazid, ethambutol, pyrazinamide (RHEZ) administered for 26 weeks.
Eligible participants for this study have a diagnosis of pulmonary DS-TB. This is a Phase 2b/c multicenter, open-label, randomized, dose-finding study, consisting of up to 26 weeks of treatment period. Following a screening period of up to 14 days, eligible participants will be randomized in the study. Randomization will be stratified by presence of bilateral cavitation on screening chest x-ray (yes or no). After the end of the treatment period, participants will be followed until 12 months post randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
122
Delamanid (300 mg QD) + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (10 mg QD) for 17 weeks
Delamanid (300 mg QD\] + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (30 mg QD) for 17 weeks
Delamanid (300 mg QD) + Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) + OPC-167832 (90 mg QD) for 17 weeks
Aurum Institute - Tembisa Clinical Research Centre
Tembisa, Gauteng, South Africa
TASK Applied Science, Brooklyn Chest Hospital Premises
Cape Town, South Africa
University of CapeTown Lung Center Institute
Cape Town, South Africa
Themba Lethu Clinic Clinical HIV Research Unit (CHRU)
Johannesburg, South Africa
Incidence of Treatment Emergent Adverse Events
Incidence of TEAEs: all TEAEs, TEAEs by severity, TEAEs potentially causally related to the IMP or trial medication, TEAEs with an outcome of death or trial medication, Serious TEAEs, TEAEs leading to discontinuation of the IMP or trial medication
Time frame: Baseline to 12 months post randomization
Incidence of potentially clinically significant changes of laboratory tests from baseline and abnormalities in the vital signs, physical examinations, electrocardiograms (ECGs) at each visit were assessed and at end of study.
Incidence of potentially clinically significant changes from baseline and abnormalities in the parameters below, at each visit were assessed and at end of study: Lab Tests: Hematology, Clinical Chemistry, CD4 Count, Urinalysis Vital Signs: systolic and diastolic blood pressure (mmHg), heart rate (beats/min), respiratory rate (breaths/min), body temperature (C), weight (kg) and body mass index (kg/m2) Physical exam include examination of the abdomen; extremities; head, eyes, ears, nose (HEENT); neurological; skin and mucosae; thorax; urogenital; audiometry assessment and visual assessment. ECGs: ECG PR interval (msec) ECG QTc interval (msec) ECG arrhythmia
Time frame: Baseline to 12 months post randomization
Number of participants with a grade 3 or higher AE
The proportion of subjects with a grade 3 or higher AE
Time frame: Baseline to 12 months post randomization
Number of all cause Treatment Discontinuation
Rate of All Cause Treatment Discontinuation
Time frame: Baseline to 12 months post randomization
Sputum culture conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT)
The proportion of subjects achieving sputum culture conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) (Sputum culture conversion occurs when a subject has the first of 2 visits of at least 1 week apart (±4 days) with sputum cultures negative and without a positive sputum culture result in between).
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RHEZ for 8 weeks followed by 18 weeks of rifampin and isoniazid (for a total of 26 weeks)
Perinatal HIV Research Unit Tshepong Hospital Complex
Klerksdorp, South Africa
Setshaba Research Center
Pretoria, South Africa
Time frame: Baseline to End of Treatment Period - Week 17 and Week 26
Proportion of participants who achieve SCC in MGIT by 8 weeks of treatment
Proportion of subjects who achieve SCC.
Time frame: Baseline to Week 8
Time to detection of MGIT cultures
Change in time to detection, in days, of MGIT liquid culture results
Time frame: Baseline to 12 months post randomization
Proportion of participants who convert sputum LAM to negative by 8 weeks of treatment and by end of treatment
The proportion of subjects who convert sputum LAM concentrations from positive to negative by 8 weeks of treatment and by end of treatment
Time frame: End of Treatment Period - Week 17 and Week 26
Proportion of participants who develop drug resistance
Proportion of subjects whose sputum cultures test "resistant" to any drugs in the treatment regimens during the treatment period.
Time frame: Baseline to 12 months post randomization
Time to Sputum Culture Conversion (SCC) of each treatment group.
To compare time to SCC, in days, of each treatment group.
Time frame: Baseline to 12 months post randomization