NCT06435026

Optimizing PrEP Regimens for Pregnant Women in Sub-Saharan Africa (O-PrEP Study) - Stage 1

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: Female
• Age: 16 Years
• Healthy volunteers: Accepted

Summary

This study aims: (1) to determine the optimal dose of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for daily oral pre-exposure prophylaxis (PrEP) during pregnancy based on drug pharmacokinetics, and (2) evaluate the maternal and infant safety of increased FTC/TDF doses during these periods.

Detailed description

This is a staged study to assess the pharmacokinetics (PK) and safety of increased FTC/TDF doses for PrEP during pregnancy: STAGE 1-Dose Identification: Phase 2a pharmacokinetic (PK) study. Using an intensive sampling approach, the following detailed PK information about three doses of daily oral PrEP in pregnancy will be collected: standard FTC/TDF dose (200mg/300mg, n=18), 150% standard dose (300mg/450mg, n=18), and 200% standard dose (400mg/600mg, n=18). Following a lead-in period-where participants receive PrEP for 14 days under direct observation to reach steady state concentrations-plasma, peripheral blood mononuclear cells (PBMC), and other specimens are collected over a 24-hour period to characterize key PK parameters. During pregnancy, two cycles will be performed (i.e., during the second and third trimester) at the assigned FTC/TDF dose. For all participants, this cycle will be repeated at 12 weeks postpartum using the standard FTC/TDF dose, providing a within-person non-pregnant comparator in the longitudinal assessment of bioequivalence. Standard dose FTC/TDF will be offered between periods of direct observation. INTERMEDIARY STEP-Independent Review: Findings from the initial dose identification stage will be independently reviewed by the Study Monitoring Committee. Based on assessments of the PK, tolerability and preliminary safety data, the committee is expected to recommend an increased dosage of FTC/TDF (150% vs. 200% standard dose) for further investigation in Stage 2. STAGE 2-Extended Safety Assessment: Phase 2b open-label randomized trial. In the second stage, the extended safety of increased dose PrEP that was identified via independent review will be assessed. Comparison of standard vs. increased FTC/TDF dosages via an open-label randomized trial of 112 pregnant women, allocated 1:1 will be done. Because safety is inextricably linked to adherence, direct observation will be used to confirm adherence, but extend the exposure period through the remainder of pregnancy. Maternal safety will be assessed using detailed medical histories, symptoms diaries, and routine laboratory screening. Information about fetal growth, birth outcomes, and infant growth will be collected; and assessment of maternal and infant bone mineral density will be done twice in the early postpartum period. Embedded in this second stage is population PK sampling (i.e., in plasma, PBMCs, dried blood spot (DBS), and cervicovaginal fluid) to inform models of FTC/TDF concentrations over the course of pregnancy, to be developed as part of this study (Aim 3). Again, following the period of directly observed PrEP at the assigned dose in pregnancy, standard dose FTC/TDF will be self-administered postpartum, in accordance with local HIV guidelines. \*\* In this record, only activities related to Stage 1 of the study are described. When this advances to Stage 2, a separate entry record in clinicaltrials.gov will be created. \*\*

Conditions

• HIV
• Prevention
• Pregnancy

Interventions

Type	Name	Description
DRUG	FTC/TDF 200mg/300mg	Standard Dose
DRUG	FTC/TDF 300mg/450mg	150% Standard Dose
DRUG	FTC/TDF 400mg/600mg	200% Standard Dose

Timeline

• Start date: 2024-06-18
• Primary completion: 2026-02-11
• Completion: 2026-02-11
• First posted: 2024-05-30
• Last updated: 2026-02-17

Locations

2 sites across 2 countries: Malawi, Zimbabwe

Regulatory

• FDA-regulated drug study