Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

NCT06281834 | Recruiting Phase 1

• 1 other identifier: 2024P000306
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pediatric HIV Infection; Latent Tuberculosis

Keywords

Pediatric HIV; rifapentine; TB prevention

Outcome Measures

Primary Outcomes (1)

• 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.

  Weeks 4 and 6

Secondary Outcomes (2)

• Rifapentine AUC

  weeks 6 and 7

• Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events

  Week 48

Study Arms (1)

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.

Drug: Rifapentine; Drug: Dolutegravir

Interventions

Rifapentine 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 PK during weekly rifapentine/isoniazid for TB prevention

Dolutegravir 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

Dolutegravir PK during weekly rifapentine/isoniazid for TB prevention

Eligibility Criteria

• Age: 4 Weeks - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• (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).

You may not qualify if:

• (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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• APIN Public Health Initiatives: collaborator
• University of Cape Town: collaborator

Study Sites (1)

University College Hospital

Ibadan, Oyo State, Nigeria, Nigeria

RECRUITING

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

rifapentine; dolutegravir

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Officials

• Holly Rawizza, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Holly Rawizza, MD, MPH

CONTACT

617-432-4686; hrawizza@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Prospective single-arm, open-label, pharmacokinetic and safety study

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: February 28, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: After all data are analyzed and results are published.
• Access Criteria: At the request of researchers de-identified data may be shared.

Locations

NG (1)