PK of TAF and TDF for PrEP in Pregnant and Postpartum Women

NCT04937881 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CO-US-412-6091
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study will establish benchmarks of TFV-DP concentrations as measures of adherence following daily dosing with Tenofovir Alafenamide (TAF) compared with Tenofovir Disoproxil Fumarate (TDF) during pregnancy and postpartum. Study Investigators will recruit from an ongoing observational cohort study in Cape Town, South Africa, PrEP-PP (recruitment ongoing through July, 2021; NIMH R01MH116771; PI Coates \& Myer). Findings form this PK sub-study will be used to inform future PrEP in pregnancy and postpartum studies and develop benchmarks of the relative PK between TDF and TAF.

Conditions

Hiv

Keywords

pre-exposure prophylaxis; PrEP; pregnancy; postpartum; HIV prevention; pharmacokinetics; TAF; TDF

Outcome Measures

Primary Outcomes (2)

• Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP

  Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in pregnancy. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.

  8 week period during Pregnancy

• Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP

  Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in postpartum period. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.

  8 week period during Postpartum (up to 1 year from baseline pregnancy visit)

Secondary Outcomes (1)

• Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women

  Pregnancy (TVF-DP measures via DBS collected weekly, reported 8 weeks after start of pregnancy observation); Postpartum (TVF-DP measures via DBS collected weekly, reported 8 weeks after start of postpartum observation, up to 1 year from baseline).

Study Arms (2)

TAF arm

EXPERIMENTAL

Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period

Drug: Tenofovir alafenamide

TDF arm

ACTIVE COMPARATOR

Fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period

Drug: Tenofovir Disoproxil Fumarate

Interventions

Tenofovir alafenamide DRUG

Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)

Also known as: TAF

TAF arm

Tenofovir Disoproxil Fumarate DRUG

Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)

Also known as: TDF or Truvada

TDF arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old
• confirmed HIV-negative (confirmed with a 4th generation antigen HIV test) at time of study entry
• intend on giving birth in the MOU facility
• confirmed to be 14-24 weeks pregnant
• without psychiatric or medical contraindications to PrEP
• estimated creatinine clearance (CrCI) \>60mL/min
• resides close to clinic (\<10km)
• has a smart phone that can take video footage (with data bundle from study)
• agrees to provide video phone footage of taking a pill a day for 8 weeks during pregnancy and again for 8 weeks in postpartum period

You may not qualify if:

• Individuals not meeting the above criteria or meeting any of the following criteria will be excluded:
• Concurrent enrolment in another HIV-1 vaccine or prevention trial
• History of renal disease
• Current clinical diagnosis of hypertension
• Exhibiting psychotic symptoms
• Currently or history of taking an anti-psychotic medication
• Positive Hepatitis B surface antigen (HBsAg) test on screening
• History of bone fracture not related to trauma
• Any other medical, psychiatric or social condition which in the opinion of the investigators would affect the ability to consent and/or participate in the study
• Any maternal or fetal complication, obstetric or medical, detected during routine care or study procedures that requires referral of pregnant or postpartum women/infants to secondary or tertiary obstetric or medical care.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• University of Cape Town: collaborator
• Desmond Tutu HIV Foundation: collaborator
• Gilead Sciences: collaborator

Study Sites (1)

Gugulethu Midwife Obstetric Unit

Cape Town, South Africa

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

tenofovir alafenamide; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dvora Joseph Davey
• Organization: UCLA

dvoradavey@ucla.edu

3107011526

Study Officials

• Landon Myer, MD

  UCT

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Epidemiology

Model Details: This phase III study is a randomised control trial (RCT) of up to 60 pregnant women who will be recruited at first antenatal visit (ANC) from the Gugulethu Midwife and Obstetrics Unit. Participants will be randomized into the TDF vs TAF arm: TDF Arm: Women will receive a fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) administered once daily under direct observation for 8 weeks during pregnancy and again for 8 weeks in postpartum period TAF Arm: Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) administered once daily under direct observation for 8 weeks during pregnancy and again for 8 weeks in postpartum period Women will provide their own controls, providing pregnant and postpartum samples.

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 24, 2021
• Study Start: June 13, 2022
• Primary Completion: April 17, 2023
• Study Completion: September 1, 2023
• Last Updated: September 3, 2024
• Results First Posted: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)