Tuberculosis
Conditions
Keywords
HIV, Tuberculosis, Latent Tuberculosis
Brief summary
This study aims to find the proposed dose of Rifapentine (RPT) taken once daily with Isoniazid (INH) for 28 days to prevent tuberculosis (TB). The study will take place at multiple locations and children under 13 years old will be divided into two groups: one group will include children without HIV, and the other group will include children with HIV who are on antiretroviral treatment. Up to 144 children will participate, and participants in each group will be followed for 24 weeks.
Interventions
DRUGRifapentine
Dispersible Tablet administered orally
DRUGIsoniazid
Dispersible Tablet administered orally
DRUGDolutegravir
Tablets and Tablets for oral suspension administered orally
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Cohort 1 will open to enrollment first and Cohort 2 will open following RPT dose confirmation in Cohort 1. Within each cohort, participants in all weight bands will be enrolled concurrently.
Eligibility
Sex/Gender
ALL
Age
No minimum to 13 Years
Healthy volunteers
No
Inclusion criteria
1. A parent or legal guardian must be willing and able to give written permission for the child to participate in the study. If required by local policies, the child must also be willing and able to give written assent to participate. All sites must follow local policies and procedures. 2. Age requirements at entry: * Cohort 1: Children under 13 years old. * Cohort 2: Children aged 12 weeks to under 13 years old. 3. For Cohort 1 participants under 28 days old: The child must have been born at or after 37 weeks of pregnancy, as determined by the site investigator using parent/guardian report or medical records. 4. Weight requirements at entry: * Cohort 1: 3 kg to under 45 kg. * Cohort 2: 6 kg to under 45 kg. 5. HIV status: * Cohort 1: Must be living without HIV. * Cohort 2: Must be living with HIV. 6. At risk of TB disease, defined as meeting at least one of the following: * Having close contact with someone with infectious pulmonary TB within the past six months. * A positive tuberculin skin test (TST) or, for those over two years old, a positive interferon gamma release assay (IGRA) if TST is not available. * For Cohort 2 only: Living in a high TB burden area (≥ 60 TB cases per 100,000 people per year). 7. Normal or mild (grade 1 or 2) test results for the following at screening (within 21 days before entry): * ALT (liver enzyme) * Estimated glomerular filtration rate (kidney function) * Absolute neutrophil count (white blood cells) * Hemoglobin (red blood cells) 8. For Cohort 2 participants: * Must have been on antiretroviral therapy (ART) for at least 12 weeks before entry. * Must have been on a specific ART regimen (once-daily DTG and two NRTIs) for at least 14 days before entry. * Must have used the same formulation of DTG (tablet or dispersible tablet) for at least three days before entry. * Must agree to continue the same formulation of DTG for the study duration. * Must have an HIV-1 RNA level below 200 copies/mL at screening. 9. Must intend to stay in the same area for the study duration. 10. Must have access to at least one meal per day during the 28-day treatment period.
Exclusion criteria
1. The child has active TB, confirmed by medical records, parent/guardian report, or tests during screening, indicated by: * Currently being treated for active TB. * Symptoms like poor growth, poor weight gain, weight loss, cough for at least 11 days, or fever for at least eight days. * X-ray or CT scan showing TB. * Positive TB test results (e.g., culture, Xpert MTB/RIF Ultra, Truenat M.tb, other nucleic acid tests, urine tests). 2. The child has been exposed to an adult with drug-resistant TB (resistant to Rifampicin or Isoniazid) within the past six months. 3. The child has taken the following medications: * Daily Isoniazid in the 28 days before entry. * Any prohibited medications listed in the study within three days before entry. 4. The child has any of the following conditions: * Acute or chronic hepatitis. * Allergy to Isoniazid or rifamycins. * Porphyria. * Severe peripheral neuropathy. 5. The child has severe acute malnutrition (weight-for-height/length less than -3 z-scores of WHO standards). Note: Children who are stunted (height-for-age more than two standard deviations below WHO standards) are eligible. 6. For Cohort 2: The child has an active AIDS-defining opportunistic infection. 7. The child has started menstruation. 8. The child has taken NVP, EFV, lopinavir/ritonavir, and/or raltegravir within 14 days before entry. 9. The child has received long-term immunosuppressive therapy (more than eight days) within 30 days before entry. Note: Short courses of steroids (seven days or less) may be allowed with approval. 10. The child is a result of a multiple birth (e.g., twins, triplets). 11. The child has any other significant medical condition that would make participation unsafe, complicate data interpretation, or interfere with study objectives, as determined by the site investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentration of Rifapentine (RPT) at specified time points among children with and without HIV | Through Day 28 |
| Area Under the Curve (AUC)(0-inf) of RPT | Through Day 28 |
| Maximum serum concentration (C(max)) of RPT | Through Day 28 |
| Half-life (t1/2) of RPT | Through Day 28 |
| Apparent oral clearance (CL/F) of RPT | Through Day 28 |
| Apparent oral volume of distribution (V/F) of RPT | Through Day 28 |
| Absorption rate (ka) of RPT | Through Day 28 |
| Trough serum concentration (C(trough)) of DTG (Cohort 2 only) | At study entry, Day 28 and Day 42 |
| CL/F of DTG (Cohort 2 only) | At study entry, Day 28 and Day 42 |
| Proportion of participants experiencing Adverse Events (AEs) | Through Day 28 |
| Proportion of participants experiencing Grade 3 or higher AEs | Through Day 28 |
| Proportion of participants experiencing Grade 2 or higher AEs assessed as related to 1HP | Through Day 28 |
| Proportion of participants experiencing Serious Adverse Events (SAEs) assessed as related to 1HP | Through Day 28 |
| Proportion of participants experiencing AEs assessed as related to 1HP that led to permanent discontinuation of the regimen | Through Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative effects of significant covariates on RPT PK | Through Day 28 | Significant covariates include age, weight, sex, ethnicity, nutritional status, and HIV-1 status |
| Proportion of participants experiencing AEs | Through Day 168 | — |
| Proportion of participants experiencing Grade 3 or higher AEs | Through Day 168 | — |
| Proportion of participants experiencing Grade 2 or higher AEs assessed as related to 1HP | Through Day 168 | — |
| Proportion of participants experiencing SAEs assessed as related to 1HP | Through Day 168 | — |
| Participant and/or parent/guardian reported palatability and acceptability of 1HP regimen | At Day 1, Day 14, and Day 28 | — |
| Number of occurrences of permanent discontinuation of 1HP regimen due to participant refusal to take 1HP or participant's parent/guardian decision to prematurely discontinue 1HP regimen | Through Day 168 | — |
| Participant adherence to the 1HP regimen | Through Day 28 | Defined as having maintained at least 85% adherence to the 1HP regimen (24 doses) measured by observed and confirmed dosing and participant/parent/guardian report. |
| Proportion of participants experiencing Grade 2 or higher AEs assessed as related to DTG (Cohort 2 only) | Through Day 42 | — |
| Proportion of participants experiencing SAEs assessed as related to DTG (Cohort 2 only) | Through Day 42 | — |
| Proportion of participants experiencing AEs assessed as related to DTG that led to permanent discontinuation of the regimen (Cohort 2 only) | Through Day 42 | — |
| Number of participants with HIV-1 RNA less than 200 copies/mL (Cohort 2 only) | At Day 42 | — |
Countries
Botswana, Haiti, Kenya, Thailand, Uganda, Zimbabwe
Contacts
CONTACTIMPAACT ClinicalTrials.gov Coordinator
CONTACTSarah Bradford
Outcome results
None listed