Clinical trial

Safety and Tolerability of 1 Month Daily (1HP) and 3 Months Weekly (3HP) Isoniazid and Rifapentine With Pharmacokinetics of Dolutegravir (DTG) in Pregnant People With HIV

NCT05122026

Name

IRB00299011

Description

Open-label, two-arm, randomized multicenter study to investigate the safety, tolerability, and pharmacokinetics (PK), and potential interactions between dolutegravir (DTG) and rifapentine (RPT) during pregnancy in people with HIV when RPT is given with isoniazid (INH) daily for 4 weeks (1HP) or weekly for 3 months (3HP) as part of tuberculosis (TB) preventive therapy (TPT). Adults (age ≥18) who are pregnant with a singleton pregnancy (confirmed by ultrasound) at a gestational age of 20-34 weeks and virally suppressed on an existing DTG-based plus two nucleoside reverse transcriptase inhibitors (NRTI) antiretroviral (ART) regimen for at least four weeks may participate.

Trial arms

Trial start

2024-01-17

Estimated PCD

2024-12-31

Trial end

2025-03-31

Status

Recruiting

Phase

Early phase I

Treatment

Rifapentine

As included in arm/group description

Arms:

Arm 1: One month of daily isoniazid and rifapentine (4 weeks), Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks)

Other names:

Priftin

Isoniazid

As included in arm/group description

Arms:

Arm 1: One month of daily isoniazid and rifapentine (4 weeks), Arm 2: Three months of once-weekly isoniazid and rifapentine (12 weeks)

Other names:

Winthrop Isoniazid

Size

252

Primary endpoint

Mortality

from study entry at Week 0 through post partum Week 24, to be reported at end of trial

Targeted serious adverse events (SAEs)

from study entry at Week 0 through post partum Week 12, to be reported at end of trial

PK sampling of Dolutegravir - Cl/F parameter

PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

PK sampling of Dolutegravir - AUC parameter

PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

PK sampling of Dolutegravir - Ctau parameter

PK sampling at Week 1 (Day 1) and Week 3 (Day 17) for both groups, and at Week 8 (Day 52) for Group 2 (3HP arm), to be reported at end of trial

Eligibility criteria

Inclusion Criteria: 1. Age \> 18 years 2. Weight \> 50 kg 3. Documented HIV infection 4. At least 4 weeks of ART and virally suppressed on dolutegravir plus two NRTIs 5. Undetectable HIV-1 viral load 6. Pregnancy at 20-34 weeks as confirmed by ultrasound 7. Singleton pregnancy Exclusion Criteria: 1. Confirmed or suspected TB disease 2. Likely to move from the study area during the study period 3. Known exposure to pulmonary TB cases with known or suspected resistance to isoniazid or rifampicin in the source case 4. TB treatment within the past year 5. TB preventive therapy within the last year 6. Sensitivity or intolerance to isoniazid or rifamycins 7. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens 8. Suspected acute hepatitis or known chronic liver disease; HBsAg positivity; severe hepatic impairment 9. Alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN) 10. Total bilirubin ≥ 2.5 times the ULN 11. Absolute neutrophil count (ANC) \< 750 cells/mm3 12. Creatinine clearance \< 50 ml/min 13. Self-reported alcohol use exceeding 21 units per week 14. Karnofsky status \< 80 15. On prohibited medications e.g. dofetilide

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomized 1:1 to receive either 1HP or 3HP', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 252, 'type': 'ESTIMATED'}}

Updated at

2024-03-18

1 organization

2 products

3 indications

Organization

Product

Indication

Indication

Indication

Product