Tuberculosis
Conditions
Interventions
All children will be on intervention arm
Clofazimine and Moxifloxacin new dispersible formulations
Sponsors
Stellenbosch University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 0 to <15 years of age 2. Confirmed or clinically diagnosed pulmonary or extrapulmonary RR-TB Confirmed with RR-TB - A diagnosis of TB based on a combination of the presence of symptoms consistent with TB (pulmonary or extrapulmonary) and/or a chest radiograph (or other radiological investigation) considered suggestive of TB AND - Microbiological confirmation of M. tuberculosis from any clinical specimen by either culture or molecular methods (including Xpert MTB/RIF or Xpert MTB/RIF Ultra and/or other approved molecular tests); AND - Rifampicin resistance demonstrated by genotypic (molecular) or phenotypic methods; AND - A clinical decision has been made to treat the child for RR-TB Clinically diagnosed with RR-TB - A presumptive diagnosis of TB based on a combination of the presence of symptoms consistent with TB (pulmonary or extrapulmonary) and/or a chest radiograph (or other radiological investigation) considered suggestive of TB AND - Documented exposure to a source case with bacteriologically confirmed intrathoracic, rifampicin-resistant TB*; AND - A clinical decision has been made to treat the child for RR-TB A TB source case with microbiologically confirmed intrathoracic TB is defined as a person (case) with intrathoracic TB, with or without extrapulmonary TB, with microbiological confirmation of M. tuberculosis from any clinical specimen by either culture or molecular methods (including Xpert MTB/RIF or Xpert MTB/RIF Ultra), and with rifampicin drug resistance demonstrated by genotypic (molecular) or phenotypic methods, who is suspected to be responsible for transmitting M. tuberculosis to the potential participant. Documentation of source case details is expected to be available in the child’s medical records and relevant eligibility criteria will be based on review of the child’s medical records only 3. Routinely treated with both clofazimine and a fluoroquinolone as part of a RR-TB treatment regimen and on treatment for <16 weeks 4. HIV-infected
Exclusion criteria
Exclusion criteria: 1. Hemoglobin 5X the upper limit of normal (ULN) at the time of enrolment 3. Body weight 460 ms (corrected mean value of QT interval, corrected using Friderica’s method), history of familial long QT syndrome, or any other clinically significant cardiac or ECG abnormality that the investigator deems may be a risk for QT prolongation. Note: Participants must be enrolled into the study based on final ECG readings by the protocol cardiologist. The site investigator should also evaluate the ECG and document that assessment in the source documentation and manage the participant in real time based on the local read 5. Known intolerance or hypersensitivity to moxifloxacin or clofazimine 6. A condition such as clinically significant cardiac, renal, liver, neurological, neuropsyschological or any other condition that in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives 7. Use, or anticipated use, of any of the prohibited medications (see Section 5.7) within 3 days of enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameters (clearance, volume of distribution,and absorption-related parameters, and AUC, Cmax)of moxifloxacin and clofazimine in children with RR-TB, for the whole group and by age categories (0-2,2-5 and 5-12 years) and weight bands (above andbelow 15 kg) per formulation (i.e. PK samplingoccasion). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety and tolerability endpoints a. Cumulative incidence of AEs of any grade using DAIDS tables for grading the severity of adverse events version 2.1March 2017), which are at least possibly related to moxifloxacin or clofazimine, through RR TB treatment completion or study completion b. Cumulative incidence of = Grade 3 AEs (which are at least possibly related to moxifloxacin or clofazimine),through RR-TB treatment completion or study completion c. Cumulative incidence of QT interval prolongation and change in QTcF (ms) over the study period in relation to moxifloxacin and clofazimine concentrations. d. Proportion of participants with moxifloxacin or clofazimine treatment limiting AEs through RR-TB treatment completion or study completion. 2. Dosing algorithm derived by simulation of optimal moxifloxacin and clofazimine doses in children, using nonlinear mixed effects models, and an age and/or weight banding approach. 3. Plasma PK parameters of moxifloxacin and clofazimine in children routinely treated for RR-TB by age, weight, nutritional status (WAZ and HAZ), formulation and other key covariates. 4. Descriptive summaries and qualitative descriptions of acceptability (including palatability) of treatment regimens and moxifloxacin and clofazimine formulations relative to patient and caregiver social contexts. 5. Direct and indirect health system and household costs associated with treatment of RR-TB, overall and using new formulations | — |
Countries
South Africa
Contacts
Public ContactTina Sachs
Project Manager
Outcome results
None listed