Pediatric HIV InfectionPhase 1NCT06281834
Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention
A Phase 1 study testing Rifapentine and Dolutegravir in people with Pediatric HIV Infection and Latent Tuberculosis, run by Brigham and Women's Hospital at 1 site in Nigeria.
Trial summary
Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Read more about this study
- Who is it for?
- Ages 4 weeks to 11 years
- Conditions the study is for
- Pediatric HIV Infection, Latent Tuberculosis
- What is being tested?
- Rifapentine and Dolutegravir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteNigeria
- Study dates
- 15 Nov 2024to 1 Jun 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 weeks to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- (1) ART-naïve or ART-experienced HIV-infected children 4 weeks to <12 years of age;
- (2) no evidence of active TB based on an appropriate clinical evaluation;
- (3) negative TB diagnostic test if performed (other than tuberculin skin testing);
- (4) weight of at least 4 kilograms; and
- (5) consent of the parent or legal guardian and assent of the child (if ≥7 years of age).
Who cannot join
- (1) Baseline labs with evidence of ≥grade 3 abnormalities: alanine aminotransferase (ALT), total bilirubin, absolute neutrophil count (ANC), platelets, creatinine;
- (2) presenting with acute respiratory distress or decompensation, or any clinical syndrome which could suggest undiagnosed TB or other opportunistic infection; or
- (3) receipt of a medication that has drug-drug interactions with DTG or RPT.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nigeria1 site, 1 recruiting
- Recruiting
University College Hospital
Ibadan, Oyo State, Nigeria
Regina Oladokun, MD, 16172305959, ginaolad@gmail.com
About this study
Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Short-course TB prevention/latent TB infection (LTBI) treatment regimens increase completion rates but have not been adequately studied among children living with HIV. Our prospective, open-label PK study will examine and extend use of weekly rifapentine and isoniazid (3HP) among children receiving dolutegravir. This will address gaps in knowledge by examining two-way PK of short-course LTBI treatment in a vulnerable pediatric population.
Read the detailed description
This study is a prospective, single-arm, open-label, intensive and sparse pharmacokinetic (PK) and safety study to evaluate steady-state dolutegravir (DTG) and rifapentine (RPT) concentrations among 25 ART-naïve or experienced children living with HIV who screen negative for TB in two age categories. Study design differs by age cohort since RPT dosing is well-established for children ≥2 years of age but not for children <2 years. Children 2-11 years receive standard weekly rifapentine/isoniazid (3HP) dosing for a 12-week course, a World Health Organization (WHO)-recommended LTBI treatment option. For young children <2 years of age, intensive PK will be evaluated after a single-dose of extrapolated weekly rifapentine/isoniazid (RPT/INH), followed by standard WHO-recommended LTBI prophylaxis (isoniazid daily).
Children will be recruited from two large pediatric HIV clinics in Nigeria. Children 2-11 years will receive HIV treatment that is considered standard of care consisting of weight-based DTG once daily along with two non-nucleoside reverse transcriptase inhibitors (NRTIs), plus 3HP at standard doses for LTBI treatment. Children <2 years of age also receive standard DTG-based ART as well as standard isoniazid (INH) prophylaxis for LTBI, however, they will additionally receive a single dose of weekly RPT/INH for study purposes. The primary study intervention is, therefore, additional blood sampling for drug concentration determination (both DTG and RPT) and biomarker assessment. Clinical and laboratory monitoring for toxicity occur throughout the 48 week study period.
PK sampling for drug concentration determination will occur at three time points during the 48-week study. Specifically, intensive PK sampling will occur at study week 6, while sparse PK sampling will occur at weeks 4 and 7. Additionally, the endogenous biomarker of CYP3A4 activity, 4-beta-hydroxycholesterol to cholesterol ratio, will be evaluated to advance understanding of underlying mechanisms of drug action. Blood sampling to quantify this biomarker will occur at either 4 (among ART-experienced children) or 5 (ART-naive) time points during the 48-week study.
- Conditions
- Pediatric HIV Infection, Latent Tuberculosis
- Being tested
- Rifapentine, Dolutegravir
- Keywords
- Pediatric HIV, rifapentine, TB prevention
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifapentineDrug
Children 2-11 years received standard HIV treatment and 3HP (RPT/INH weekly for 12 weeks) for TB prevention. Children <2 years receive standard HIV treatment, a single-dose of extrapolated weekly RPT/INH, followed by standard INH prophylaxis. Safety and pharmacokinetics will be evaluated.
DolutegravirDrug
All children in this study are living with HIV and thus dolutegravir is a standard part of treatment; in this study we will collect blood samples to measure dolutegravir levels during combination treatment with rifapentine/isoniazid treatment for TB prevention
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir PK during weekly rifapentine/isoniazid for TB prevention | Experimental | This is a single arm study: all patients are started on standard HIV treatment, with LTBI/TB prevention treatment varying according to age cohorts. Children 2-11 years receive standard weekly rifapentine/isoniazid (3HP) for TB prevention; those <2 years received a single-dose of extrapolated weekly RPT/INH, followed by standard INH prophylaxis. Receives: Drug: Rifapentine; Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dolutegravir AUC during weekly rifapentine/isoniazid
Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature. Intensive PK sampling will occur at week 6 for dolutegravir and rifapentine PK. Week 4 sparse PK sampling will provide dolutegravir exposures without rifapentine.
Measured: Weeks 4 and 6
Secondary outcomes (2)
Rifapentine AUC
Rifapentine AUC will be compared against adult targets. Week 7 sparse PK will provide weekly Cmin estimate.
Measured: weeks 6 and 7
Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events
Laboratory and clinical toxicities are monitored at 8-9 time points throughout the study and the proportion of children experiencing severe adverse events will be determined.
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start15 Nov 2024
- Primary completion1 Feb 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric HIV InfectionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective single-arm, open-label, pharmacokinetic and safety study
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- APIN Public Health Initiatives, University of Cape Town
- Responsible party
- Principal investigator, Holly Rawizza, M.D., M.P.H., Brigham and Women's Hospital
- Investigators
- Holly Rawizza, MD, MPH, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06281834
- Sponsor's protocol ID
- 2024P000306
- Status last verified
- Jul 2026
- First submitted
- 16 Feb 2024
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: At the request of researchers de-identified data may be shared.