Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT06281834 |
Other study ID # |
2024P000306 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
May 2024 |
Est. completion date |
June 2027 |
Study information
Verified date |
February 2024 |
Source |
Brigham and Women's Hospital |
Contact |
Holly Rawizza, MD, MPH |
Phone |
617-432-4686 |
Email |
hrawizza[@]bwh.harvard.edu |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical 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. 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.
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.