Clinical trial

Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

Name

2024P000306

Description

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.

Trial arms

Trial start

2024-05-01

Estimated PCD

2027-02-01

Trial end

2027-06-01

Status

Not yet recruiting

Phase

Early phase I

Treatment

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.

Arms:

Dolutegravir PK during weekly rifapentine/isoniazid for TB prevention

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

Arms:

Dolutegravir PK during weekly rifapentine/isoniazid for TB prevention

Size

Primary endpoint

Dolutegravir AUC during weekly rifapentine/isoniazid

Weeks 4 and 6

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Prospective single-arm, open-label, pharmacokinetic and safety study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 25, 'type': 'ESTIMATED'}}

Updated at

2024-02-28

1 organization

2 products

2 indications

Organization

Brigham and Women's Hospital

Product

Rifapentine

Indication

Pediatric HIV infection

Indication

Tuberculosis

Product

Dolutegravir