Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06435026
Status:
RECRUITING
Last Update Posted:
2024-05-30
First Post:
2024-05-20
Brief Title:
Optimizing PrEP Regimens for Pregnant Women in Sub-Saharan Africa O-PrEP Study - Stage 1
Sponsor:
University of North Carolina Chapel Hill
Organization:
University of North Carolina Chapel Hill
Study Overview
Official Title:
Optimizing PrEP Regimens for Pregnant Women in Sub-Saharan Africa O-PrEP Study - Stage 1
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study aims 1 to determine the optimal dose of emtricitabinetenofovir disoproxil fumarate FTCTDF for daily oral pre-exposure prophylaxis PrEP during pregnancy based on drug pharmacokinetics and 2 evaluate the maternal and infant safety of increased FTCTDF doses during these periods
Detailed Description:
This is a staged study to assess the pharmacokinetics PK and safety of increased FTCTDF 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 FTCTDF dose 200mg300mg n18 150 standard dose 300mg450mg n18 and 200 standard dose 400mg600mg n18 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 ie during the second and third trimester at the assigned FTCTDF dose For all participants this cycle will be repeated at 12 weeks postpartum using the standard FTCTDF dose providing a within-person non-pregnant comparator in the longitudinal assessment of bioequivalence Standard dose FTCTDF 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 FTCTDF 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 FTCTDF dosages via an open-label randomized trial of 112 pregnant women allocated 11 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 ie in plasma PBMCs dried blood spot DBS and cervicovaginal fluid to inform models of FTCTDF 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 FTCTDF 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 clinicaltrialsgov will be created
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 FTCTDF dose 200mg300mg n18 150 standard dose 300mg450mg n18 and 200 standard dose 400mg600mg n18 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 ie during the second and third trimester at the assigned FTCTDF dose For all participants this cycle will be repeated at 12 weeks postpartum using the standard FTCTDF dose providing a within-person non-pregnant comparator in the longitudinal assessment of bioequivalence Standard dose FTCTDF 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 FTCTDF 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 FTCTDF dosages via an open-label randomized trial of 112 pregnant women allocated 11 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 ie in plasma PBMCs dried blood spot DBS and cervicovaginal fluid to inform models of FTCTDF 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 FTCTDF 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 clinicaltrialsgov will be created
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01AI157859 | NIH | None | httpsreporternihgovquickSearchR01AI157859 |