Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

NCT ID: NCT06281834

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-15

Study Completion Date

2027-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Pediatric HIV Infection Latent Tuberculosis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Pediatric HIV rifapentine TB prevention

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Prospective single-arm, open-label, pharmacokinetic and safety study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dolutegravir PK during weekly rifapentine/isoniazid for TB prevention

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.

Group Type EXPERIMENTAL

Rifapentine

Intervention Type DRUG

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.

Dolutegravir

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Rifapentine

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.

Intervention Type DRUG

Dolutegravir

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* (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).

Exclusion Criteria

* (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.
Minimum Eligible Age

4 Weeks

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

APIN Public Health Initiatives

UNKNOWN

Sponsor Role collaborator

University of Cape Town

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Holly Rawizza, M.D., M.P.H.

Assistant Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Holly Rawizza, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University College Hospital

Ibadan, Oyo State, Nigeria

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Nigeria

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Holly Rawizza, MD, MPH

Role: CONTACT

Phone: 617-432-4686

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Regina Oladokun, MD

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024P000306

Identifier Type: -

Identifier Source: org_study_id