Tuberculosis, HIV Infections
Conditions
Brief summary
This Phase I/II study evaluated the pharmacokinetics, safety, and tolerability of the anti-tuberculosis (TB) drug delamanid (DLM) in combination with an optimized multidrug background regimen (OBR) for multidrug-resistant tuberculosis (MDR-TB) in children with MDR-TB with and without HIV.
Detailed description
The purpose of this study was to evaluate the pharmacokinetics, safety, and tolerability of the anti-TB drug DLM in combination with OBR for MDR-TB in children with MDR-TB with and without HIV. Participants were enrolled in one of four age cohorts: 12 to less than 18 years, 6 to less than 12 years, 3 to less than 6 years, or 0 to less than 3 years. All participants were to receive DLM doses according to their age group and weight for 24 weeks. Study visits occurred at study entry; Weeks 2 and 4; every 4 weeks through Week 40; and at Weeks 48, 60, 72, and 96. Visits included physical examinations; blood, urine, and sputum collection; chest x-rays; electrocardiograms (ECGs); hearing tests; medical history reviews; adherence assessments; and acceptability questionnaires.
Interventions
DRUGDelamanid
Administered orally; dosing based on participants' weight. ≥ 40 kg: 100 mg twice daily (adult formulation); 30 to \< 40 kg: 50 mg twice daily (adult formulation); 15 to \< 30 kg: 25 mg twice daily (pediatric formulation); \< 15 kg: 15 mg twice daily (pediatric formulation)
DRUGOptimized multidrug background regimen (OBR) for children with MDR-TB
Non-study prescribed OBR varied according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
\- Parent (or legal guardian) willing and able to provide written informed consent for child study participation. Additionally, for children whose assent is required per site institutional review board/ethics committee (IRB/EC) policies and procedures, child willing and able to provide written assent for his or her study participation. * HIV status determined by testing requirements in the protocol (see the protocol for more information on this criterion) * If living with HIV: Initiated the standard of care antiretroviral therapy (ART) regimen at least two weeks prior to enrollment (note: regimens including efavirenz \[EFV\], nevirapine \[NVP\], a boosted protease inhibitor \[PI\], or integrase strand transfer inhibitor \[INSTI\] are allowed) * Confirmed or probable MDR-TB classified as follows: * Confirmed MDR-TB (or rifampicin mono-resistant TB \[RMR-TB\], pre-extensively drug-resistant \[XDR\] or XDR-TB): \*Intra-thoracic (pulmonary) TB based on chest radiograph consistent with TB, and/or any of the following forms of extrathoracic TB: 1. Peripheral TB lymphadenitis 2. Pleural effusion or fibrotic pleural lesions 3. Stage 1 TB meningitis 4. Miliary and abdominal TB 5. Other non-disseminated forms of TB disease (see also exclusion criterion below) AND * Microbiological confirmation of Mycobacterium tuberculosis from any clinical specimen by either culture or molecular methods (including Xpert MTB/RIF) AND \*Drug-resistance demonstrated by genotypic (molecular) or phenotypic methods, with any of the following resistance patterns: \*MDR-TB (resistance to both rifampicin and isoniazid (INH)) * RMR-TB or where additional INH resistance has not been confirmed (i.e., isolated Xpert MTB/RIF rifampicin resistance) * Pre-XDR-TB (MDR-TB plus resistance to any fluoroquinolone) * XDR-TB (MDR-TB plus resistance to both a fluoroquinolone and at least one additional Group A drug, i.e., bedaquiline or linezolid) Note: RMR-TB, MDR-TB, pre-XDR-TB and XDR-TB are therefore collectively referred to as "MDR-TB" for the purposes of the protocol * Probable MDR-TB (or RMR, pre-XDR or XDR-TB), with inclusion of intrathoracic and/or extrathoracic TB as listed below: \*A presumptive diagnosis of intrathoracic (pulmonary) TB based on well-documented clinical symptoms or signs of TB AND chest radiograph consistent with TB, and/or any of the following forms of extrathoracic TB: 1. Peripheral TB lymphadenitis 2. Pleural effusion or fibrotic pleural lesions 3. Stage 1 TB meningitis 4. Miliary and abdominal TB, 5. Other non-disseminated forms of TB disease (see also exclusion criterion below) AND * One of the following: * Exposure to a confirmed MDR-TB source case$ (RMR-TB, pre-XDR-TB, XDR-TB) * Documented failure to respond to a first-line regimen, and where adherence was well documented. AND * The clinical decision has been made to treat for MDR-TB $Confirmed MDR-TB source cases defined as a case with intrathoracic TB with or without extrathoracic TB, with microbiological confirmation of Mycobacterium tuberculosis from any clinical specimen by either culture or molecular methods (including Xpert MTB/RIF), and with drug-resistance demonstrated by genotypic (molecular) or phenotypic methods, with any of the resistance patterns described above. * Albumin level greater than 2.8 g/dL within 30 days prior to enrollment * Potassium greater than or equal to 3.4 and less than 5.6 mmol/L; magnesium greater than 0.59 mmol/L within 30 days prior to enrollment. Note: Electrolytes can be repleted and a recheck may be performed to meet eligibility criteria. The latest result should be used for eligibility determination. * BMI Z-score greater than -3 for children greater than or equal to 5 years of age; weight for length/height Z-score greater than -3 for children less than 5 years of age (using latest World Health Organization scores), at screening * Weight greater than or equal to 3 kg, at screening * Has initiated an appropriate optimized background regimen (OBR) MDR-TB treatment regimen as per routine treatment decision, at least two weeks but not more than eight weeks prior to enrollment, and in the opinion of the site investigator, is tolerating the regimen well at enrollment. Note: An appropriate OBR MDR-TB treatment regimen is defined as including components based on the sensitivities of the infecting isolate, if known, and past treatment history, if known. This regimen should also follow the OBR MBR-TB treatment guidelines as described in the protocol. * If male and engaging in sexual activity that could lead to pregnancy of the female partner: Agrees to use a barrier method of contraception (i.e. male condom) throughout the first 28 weeks on study (i.e., until four weeks after discontinuation of DLM). * If female and of reproductive potential, defined as having reached menarche and not having undergone a documented sterilization procedure (hysterectomy, bilateral oophorectomy, or salpingectomy): Negative pregnancy test at screening within 14 days prior to enrollment. * If female, of reproductive potential (as defined in the protocol), and engaging in sexual activity that could lead to pregnancy: Agrees to avoid pregnancy and to use one of the following forms of birth control while receiving DLM and for one month after stopping DLM: condoms, diaphragm or cervical cap, intrauterine device (IUD), hormonal-based contraception. The selected method must be initiated prior to enrollment.
Exclusion criteria
* Known allergy to any nitroimidazoles or nitroimidazole derivatives * Active use of prohibited medications listed in the protocol, within 3 days of enrollment * Participant has a history of any of the following, as determined by the site investigator or designee based on parent/guardian report and available medical records: * A significant cardiac arrhythmia that requires medication or a history of heart disease (heart failure, coronary artery disease) that increases the risk for Torsade de Pointes * Significant gastrointestinal (GI), metabolic, neuropsychiatric, kidney or endocrine disease at screening that would, in the investigator's opinion, preclude safe participation in the trial and/or assessment of primary endpoints * Previous DLM or pretomanid exposure * Note: Participants can have received up to 17 days of DLM prior to enrollment * Abnormal electrocardiogram (ECG) (including QTcF \[mean value of QT interval, corrected using Fredericia correction, on ECG performed in triplicate\] greater than or equal to 450 ms, atrioventricular block, or prolonged QRS greater than or equal to 120 ms) at screening. Note: The value from centralized ECG read should be used to determine study eligibility. * Karnofsky score less than 30% for participants greater than or equal to 16 years of age or Lansky play score less than 30% for participants less than 16 years of age, at screening * Alcohol intake that in the opinion of the study investigator could potentially interfere with study participation and/or introduce safety concerns with use of DLM * Lactating with plans to breastfeed, at enrollment * Tuberculous meningitis (TBM) Stage 2 or 3, or osteo-articular TB at screening * Co-enrolled in any other trial involving pharmacologic regimens, at screening * If exposed to HIV and less than 2 years of age: Breastfeeding at enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events of ≥ Grade 3 Severity | Measured from entry through Week 24 | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). 95% CIconfidence interval (CI) computed using exact Clopper-Pearson method. |
| Percentage of Participants With Adverse Events of ≥ Grade 3 Assessed by the Core Team to be at Least Possibly Related to the Study Drug | Measured from entry through Week 24 | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants Who Were Terminated From Study Treatment Due to a Drug-related Adverse Event | Measured from entry through Week 24 | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Entry, weeks 2, 8, 12, 16, 20, and 24 | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits were performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted if they had QTcF ≥ 500 msec at any study visit from entry to Week 24. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants Who Died Through Week 24 | Measured from entry through Week 24 | Death due to all causes included. 95% CI computed using exact Clopper-Pearson method. |
| Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter was determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The starting population PK model was developed on data from Otsuka study 232 and 233 (1). NONMEM was used when developing the final model for the population in this study. * Developed a population PK model as part of the final PK analysis * Data used in the population PK analysis included the semi-intensive PK visit (week 0, 2 and 8) and sparse PK visits (week 4, 12, 16, 24 and 28). |
| Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model The starting population PK model was developed on data from Otsuka study 232 and 233 (1). NONMEM was used when developing the final model for the population in this study. * Developed a population PK model as part of the final PK analysis * Data used in the population PK analysis included the semi-intensive PK visit (week 0, 2 and 8) and sparse PK visits (week 4, 12, 16, 24 and 28). |
| Geometric Mean of Area of Maximal Concentration (Cmax) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Geometric Mean of Area of Maximal Concentration (Cmax) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Time of Maximal Concentration (Tmax) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Time of Maximal Concentration (Tmax) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Oral Clearance (Cl/F) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Oral Clearance (Cl/F) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Volume of Distribution (Vd) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Volume of Distribution (Vd) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Mean Absorption Time (MAT) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Terminal Half-life (t1/2) DLM | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
| Median Terminal Half-life (t1/2) DM-6705 | Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose | PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events ≥ Grade 3 Severity | Measured from entry through Week 72 post DLM | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants With Adverse Events ≥ Grade 3 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug | Measured from entry through Week 72 post DLM | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec | Screening, Entry, weeks 2, 8, 12, 16, 20, 24 and week 28 | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted as having an outcome if they had QTcF ≥ 500 msec at any study visit from entry to Week 28. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants Who Died Through Week 72 Post DLM | Measured from entry through Week 72 post DLM | Death due to all causes included. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants With Adverse Events ≥ Grade 2 Severity | Measured from entry through Week 72 post DLM | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method. |
| Percentage of Participants With Adverse Events ≥ Grade 2 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug. | Measured from entry through Week 72 post DLM | At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method. |
| Count of Participants With Change in QTcF Interval From Baseline of Greater Than 60 ms | Entry, weeks 2, 8, 12, 16, 20, 24, and week 28 | Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted if they had QTcF was greater than 60 msec at any study visit from entry to Week 28. |
| Percentage of Participants (Overall) With TB Treatment Outcomes | Measured from entry through Week 72 post DLM | Site investigator assessment of participant TB treatment outcomes through last study visit were entered into the eCRF. Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol. |
| Number of Participants Who Had Permanently Discontinued Study Drug Whilst on Study Due to Intolerance or Refusal to Take Medication | Measured from entry through Week 24 | Participants were assessed for tolerability of the study drug during the study by their intolerance or refusal to take the medications |
| Frequency of Cumulative Responses to Taste of Study Drug in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. The participants had the option of taking the study drug either as dispersible tablet or tablet formulation. |
| Frequency of Cumulative Responses to Formulation of Study Drug in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. The participants had the option of taking the study drug either as dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation. |
| Frequency of Cumulative Responses to Taste of Dispersible Tablet Doses in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation. |
| Frequency of Cumulative Responses to Administration of Dispersible Tablet Doses in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation. |
| Frequency of Cumulative Responses to Taste of Tablet Doses in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation. |
| Frequency of Cumulative Responses to Administration of Tablet Doses in an Acceptability Assessment | Assessments conducted at weeks 2, 8 and 24 | Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation. |
| Age Effect on Bioavailability DLM | Approximately Week 2 | Plasma concentrations are used to determine age effect on bioavailability. The age covariate describes the fold change in bioavailability for each respective age group of 0-1 year and 1-2 years, with participants aged \>2 to \<18 years used as the reference group. Study arms were combined for the analysis of age effect. |
| Age Effect on Fraction Metabolised From Delaminid to DM-6705 | Approximately Week 2 | Plasma concentrations are used to determine age effect on bioavailability. The age covariate describes the fold change in bioavailability for each respective age group of 0-1 year and 1-2 years, with participants aged \>2 to \<18 years used as the reference group. Study arms were combined for the analysis of age effect. |
| Dose Effect on Bioavailability DLM | Approximately Week 2 | Plasma concentrations are used to determine dose effect on bioavailability. For doses \> 50 mg the bioavailability is described by F=(dose/100)-0.66. The participants receiving the dose 100 mg are the reference group and the dose effect of doses 15-20mg, 25mg and 50mg on the bioavailability are compared to the reference group and the fold change is presented. Study arms were combined for the analysis of dose effect. |
Countries
India, South Africa, Tanzania
Contacts
STUDY_CHAIRAnthony Garcia-Prats, MD
University of Wisconsin, Madison
STUDY_CHAIREthel Weld, MD
Johns Hopkins University
Participant flow
Recruitment details
The first enrollment to the study was in February 2019 and enrollment was completed in November 2024 with a total of 37 participants who initiated study drug. There enrollments were from three sites from South Africa - Desmond Tutu TB Center - Stellenbosch University, Sizwe CRS, and PHRU Matlosana CRS; one site from India - Byramjee Jeejeebhoy Govt. Med Ctr; and one site from Tanzania - Kilimanjaro Christian Medical Center.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 7.0 years |
| Height | 158 centimeter (cm) |
| HIV-1 status living with HIV-1 | 3 Participants |
| HIV-1 status not living with HIV-1 | 7 Participants |
| Race/Ethnicity, Customized Black African | 24 Participants |
| Race/Ethnicity, Customized Coloured | 7 Participants |
| Race/Ethnicity, Customized Indian (Native of India) | 0 Participants |
| Region of Enrollment India | 6 participants |
| Region of Enrollment South Africa | 10 participants |
| Region of Enrollment Tanzania | 2 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
| TB disease spectrum ExtraPulmonary TB (EPTB) | 1 Participants |
| TB disease spectrum PTB and EPTB | 0 Participants |
| TB disease spectrum Pulmonary TB (PTB) | 31 Participants |
| Weight | 26 kilogram (kg) |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 8 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 10 / 11 | 8 / 8 | 6 / 6 | 10 / 12 |
| serious Total, serious adverse events | 5 / 11 | 1 / 8 | 5 / 6 | 7 / 12 |
Outcome results
None listed