The Women TAF-FTC Benchmark Study

Sponsor

University of Washington (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05140954

Collaborator

Kenya Medical Research Institute (Other), University of Colorado, Denver (Other), Gilead Sciences (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study seeks to assess the safety and define blood and tissue benchmark concentrations of Tenofovir (TFV) and Tenofovir diphosphate (TFV-DP) in Cisgender women using directly observed tenofovir alafenamide (TAF)-emtricitabine (TAF-FTC) pre-exposure prophylaxis (PrEP). These data will help accurate interpretation of efficacy results obtained in HIV prevention trials and programs in cisgender women.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: co-formulated 25mg TAF/ 200mg FTC	Phase 2/Phase 3

Detailed Description

This is an open-label, randomized, three-arm, directly observed therapy, pharmacokinetics study. HIV-uninfected non-pregnant cisgender women will be randomly assigned to 1 of 3 dosing frequencies of directly observed therapy (DOT) TAF-FTC PrEP, to help differentiate poor and modest from perfect adherence. The primary objectives of the study are:

To describe the safety of TAF-FTC-based PrEP in HIV-unifected cisgender women.
To define the cisgender women-specific expected blood concentrations and dose-proportionality for TFV-DP in DBS and PBMCs using directly observed TAF-FTC therapy at 2, 4, 7 doses per week.
To establish a model to predict adherence rate to TAF-FTC by level of TFV-DP in DBS for cisgender women.

The study will be the first to define TAF-FTC-based PrEP adherence-blood concentration thresholds for African cisgender women, a priority population for HIV prevention. The findings will guide accurate interpretation of safety, adherence, and efficacy of planned or ongoing HIV prevention trials in African women.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Safety and Pharmacokinetics of TAF-FTC Pre-exposure Prophylaxis in Kenyan Cisgender Women

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Perfect Adherence Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC once daily (7 doses per week).	Drug: co-formulated 25mg TAF/ 200mg FTC Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC Other Names: Descovy
Experimental: Moderate Adherence Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC 4 times per week	Drug: co-formulated 25mg TAF/ 200mg FTC Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC Other Names: Descovy
Experimental: Poor Adherence Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC twice per week	Drug: co-formulated 25mg TAF/ 200mg FTC Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC Other Names: Descovy

Arm

Intervention/Treatment

Experimental: Perfect Adherence

Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC once daily (7 doses per week).

Drug: co-formulated 25mg TAF/ 200mg FTC

Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC

Other Names:

Descovy

Experimental: Moderate Adherence

Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC 4 times per week

Drug: co-formulated 25mg TAF/ 200mg FTC

Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC

Other Names:

Descovy

Experimental: Poor Adherence

Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC twice per week

Drug: co-formulated 25mg TAF/ 200mg FTC

Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 25 mg TAF/ 200mg FTC

Other Names:

Descovy

Outcome Measures

Primary Outcome Measures

Frequency of adverse events [Assessed through 16 weeks]
Describe the frequency of graded adverse events, including emergent HIV infection during the study period.
Steady state concentrations of tenofovir disphosphate (TFV-DP) for different dosing patterns of DOT TAF/FTC PrEP measured in dried blood spots (DBS) and PBMC [Assessed through 10 weeks]
Measured in DBS and PBMC

Secondary Outcome Measures

Steady state concentrations of tenofovir for different dosing patterns of DOT TAF/FTC PrEP [Assessed through 10 weeks]
Measured in plasma and vaginal tissue
Steady state concentrations of TFV-DP for different dosing patterns of DOT TAF/FTC PrEP measured in vaginal tissue [Assessed through 10 weeks]
Measured in vaginal tissue

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age ≥18 and ≤30 years old
Willing to undergo urine pregnancy tests
Has understood the information provided and has provided written informed consent before any study-related procedures are performed.
HIV uninfected based on negative HIV rapid tests, according to Kenyan national algorithm
Normal renal function (estimated glomerular filtration rate >60 mL/min)
Hepatitis B surface Ag negative
No active clinically significant medical or psychiatric conditions that, in the opinion of the investigators, would interfere with study participation
Lack of severe anemia (Hemoglobin >10 g/dL)
Willing to use DOT and come to clinic frequently for DOT PrEP for at least 10 weeks
Willing to have home visits for follow up
Has access to an active smartphone to allow off-site observation of dosing if unable to come to the clinic or as determined by the study staff, the participant resides in close location to clinic to permit home visit if unable to come to the clinic. i.e., potential participants without a smatphone may be enrolled in the study if investigator determines that the particiapnt resides within reasonable distance from the clinic that would permit home visit id the participant misses their visit.
Intention to stay within the study site's catchment area for at least 10 weeks.
Resides or works in catchment area with high speed internet coverage to permit video streaming
Not pregnant or breast feeding
Willing to use effective contraception during the study period.
At low risk for HIV. In Kenya, national guidelines define substantial risk for HIV and recommend PrEP be an option for individuals reporting: partner of HIV-infected person not on ART or on ART for <6 months, >1 partner of unknown status, transactional sex, recent STI, recurrent PEP use, inconsistent condom use, or injection drug use. So, non-pregnant cisgender women reporting any of these factors will not be eligible for the study but will be linked for PrEP at clinic of choice including at Thika Site itself.
Willing to be randomized to non-daily PrEP and come to clinic frequently for DOT PrEP
Willingness and ability to be abstinent for at least 7 days after each vaginal biopsy visit.

Exclusion Criteria:

Inability to give informed consent
Positive screening HIV+ as determined by standard rapid serologic assays or suspected acute HIV infection in the opinion of the clinician. (example signs and symptoms of acute HIV infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy cervical or inguinal)
Positive HBV surface antigen test at screening
Calculated creatinine clearance <60 ml/min.
Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.
Prohibited concomitant medications are: investigational agents (within 30 days of enrollment), aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (>800mg acyclovir or >500mg valacyclovir for >7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TAF®, TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively.
Current or past use of PrEP (pre-exposure prophylaxis)
Not willing to have home visits
Pregnancy or plan to become pregnant in the next 6 months or unwillingness to use birth control
Current breastfeeding
High risk of HIV infection (for example: sexually active with an HIV infected partner; engages in condomless intercourse with HIV-infected partners or partner of unknown status during the study; females who exchange sex for money, shelter, or gifts; active injection drug use or during the last 12 months; newly diagnosed sexually transmitted infections in last 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kenya Medical Research Institute - Partners in Health Research and Development	Thika		Kenya

Sponsors and Collaborators

University of Washington
Kenya Medical Research Institute
University of Colorado, Denver
Gilead Sciences

Investigators

Principal Investigator: Kenneth K Mugwanya, MBChB, MS, PhD, University of Washington
Principal Investigator: Peter L Anderson, PharmD, University of Colorado, Denver