HIVPhase 2NCT06435026
Optimizing PrEP Regimens for Pregnant Women in Sub-Saharan Africa (O-PrEP Study) - Stage 1
A Phase 2 study testing FTC/TDF 200mg/300mg, FTC/TDF 300mg/450mg and FTC/TDF 400mg/600mg in people with HIV and Prevention, run by University of North Carolina, Chapel Hill at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV, Prevention, Pregnancy
- What is being tested?
- FTC/TDF 200mg/300mg, FTC/TDF 300mg/450mg and FTC/TDF 400mg/600mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 18 Jun 2024to 11 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Maternal participants:
- Aged 16 years or older
- PrEP-eligible by local guidelines
- Pregnant with a viable singleton pregnancy of between 14 and 23 completed weeks of gestation (from 14 weeks + 0 days to 23 weeks + 6 days) by ultrasonography at study entry
- HIV-negative based on the study-specific screening algorithm
- Hepatitis B surface antigen (HBsAg)-negative
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- Weight >35 kg
- Provided informed consent and expressed willingness to participate in study activities with their infants, including daily administration of oral PrEP under direct observation
- Infant participants:
- Infant participants enter the study with their mother as unborn infants. There are no specific eligibility criteria for infant participation otherwise. If an infant is deemed too ill to undergo study procedures, procedures necessary for clinical management may be prioritized.
Who cannot join
- Maternal participants will not enter the study if any of the following conditions are identified during the screening process:
- Grade 2 or greater laboratory parameters for alanine transaminase (ALT) or aspartate aminotransferase (AST), hemoglobin (HB), and absolute neutrophil count (ANC).
- Estimated creatinine clearance (CrCl) 90 mL/min or below, using the Cockcroft-Gault formula.
- Known history or evidence of current significant disease process, including: hematological conditions, renal disease, unexplained bone fractures, environmental enteric dysfunction, or allergies/sensitivities to FTC/TDF.
- Other current significant or uncontrolled disease process (active or chronic), substance use, or social circumstances that, in the judgment of the site investigator, would make participation in the study inappropriate or unsafe.
- Fetuses with known or suspected major fetal anomaly, either from screening ultrasound or via medical record
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- Intention to leave the study site's catchment area before scheduled study exit.
- Current use of prohibited medications
- Concurrent use of other biomedical HIV prevention interventions (vaginal ring, injectable PrEP, any investigational prevention product).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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.
Read the 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
- Being tested
- FTC/TDF 200mg/300mg, FTC/TDF 300mg/450mg, FTC/TDF 400mg/600mg
- Keywords
- HIV, PrEP, Pregnancy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FTC/TDF 200mg/300mgDrug
Also called PrEP
Standard Dose
FTC/TDF 300mg/450mgDrug
Also called PrEP
150% Standard Dose
FTC/TDF 400mg/600mgDrug
Also called PrEP
200% Standard Dose
| Study group | Role | What they receive |
|---|---|---|
| Standard Dose | Other | daily oral FTC/TDF standard dose (200mg/300mg, n=18) Receives: Drug: FTC/TDF 200mg/300mg |
| 150% standard dose | Other | daily oral FTC/TDF dose (300mg/450mg, n=18), Receives: Drug: FTC/TDF 300mg/450mg |
| 200% standard dose | Other | daily oral FTC/TDF (400mg/600mg, n=18) Receives: Drug: FTC/TDF 400mg/600mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs)
AUC of TFV-DP
Measured: Up to 20 weeks after delivery
Secondary outcomes (2)
Maternal grade >/= 2 adverse events
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Event Grading Table), will be used to measure safety.
These include grade 2 (moderate), grade 3 (severe), and grade 4 (potentially life-threatening) events. Relatedness of adverse events will be assessed by site teams as defined in the protocol.
Measured: Up to 20 weeks after delivery
Adverse pregnancy outcomes
This is a composite outcome that includes fetal death (spontaneous abortion or stillbirth), preterm birth (<37 weeks gestation), and small for gestational age (<10%tile birthweight for gestational age according to INTERGROWTH 21st standards)
Measured: At time of delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2024
- Study start18 Jun 2024
- Primary completion11 Feb 2026
- Study completion11 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin Chi, MD, MSc, Principal investigator, University of North Carolina, Chapel HillLynda Stranix-Chibanda, MBChB, MMed, Principal investigator, University of ZimbabwePeter Anderson, PharmD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06435026
- Sponsor's protocol ID
- 22-2056
- Other IDs
- R01AI157859
- Status last verified
- Feb 2026
- First submitted
- 20 May 2024
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with University of North Carolina (UNC).
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing PrEP Regimens for Pregnant Women in Sub-Saharan Africa (O-PrEP Study) - Stage 1
- ClinicalTrials.gov ID
- NCT06435026
- Acronym / sponsor ID
- 22-2056
- Conditions
- HIV, Prevention, Pregnancy
- Keywords
- HIV, PrEP, Pregnancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 18 Jun 2024 (actual)
- Primary completion
- 11 Feb 2026 (actual)
- Study completion
- 11 Feb 2026 (actual)
- First posted
- 30 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Standard Dose | Other | Drug: FTC/TDF 200mg/300mgdaily oral FTC/TDF standard dose (200mg/300mg, n=18) |
| 150% standard dose | Other | Drug: FTC/TDF 300mg/450mgdaily oral FTC/TDF dose (300mg/450mg, n=18), |
| 200% standard dose | Other | Drug: FTC/TDF 400mg/600mgdaily oral FTC/TDF (400mg/600mg, n=18) |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Aged 16 years or older
- PrEP-eligible by local guidelines
- Pregnant with a viable singleton pregnancy of between 14 and 23 completed weeks of gestation (from 14 weeks + 0 days to 23 weeks + 6 days) by ultrasonography at study entry
- HIV-negative based on the study-specific screening algorithm
- Hepatitis B surface antigen (HBsAg)-negative
Key exclusion criteria (9 listed)
- Maternal participants will not enter the study if any of the following conditions are identified during the screening process:
- Grade 2 or greater laboratory parameters for alanine transaminase (ALT) or aspartate aminotransferase (AST), hemoglobin (HB), and absolute neutrophil count (ANC).
- Estimated creatinine clearance (CrCl) 90 mL/min or below, using the Cockcroft-Gault formula.
- Known history or evidence of current significant disease process, including: hematological conditions, renal disease, unexplained bone fractures, environmental enteric dysfunction, or allergies/sensitivities to FTC/TDF.
- Other current significant or uncontrolled disease process (active or chronic), substance use, or social circumstances that, in the judgment of the site investigator, would make participation in the study inappropriate or unsafe.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FTC/TDF 200mg/300mgAlso: PrEPStandard Dose | Drug | Standard Dose |
| FTC/TDF 300mg/450mgAlso: PrEP150% Standard Dose | Drug | 150% standard dose |
| FTC/TDF 400mg/600mgAlso: PrEP200% Standard Dose | Drug | 200% standard dose |
Primary outcome
Tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs)
Time frame: Up to 20 weeks after delivery
AUC of TFV-DP
2 secondary outcomes
Maternal grade >/= 2 adverse events
Time frame: Up to 20 weeks after delivery
Adverse pregnancy outcomes
Time frame: At time of delivery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Individual participant dataSharing planned: Yes. Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with University of North Carolina (UNC).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Chi, MD, MSc principal investigator
University of North Carolina, Chapel Hill
Lynda Stranix-Chibanda, MBChB, MMed principal investigator
University of Zimbabwe
Peter Anderson, PharmD principal investigator
University of Colorado, Denver
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FTC/TDF 200mg/300mg, FTC/TDF 300mg/450mg and FTC/TDF 400mg/600mg in people with HIV and Prevention, run by University of North Carolina, Chapel Hill at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Malawi, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) (time frame: Up to 20 weeks after delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.