NCT04760691

Pre-Exposure Prophylaxis (PrEP)- Gender Affirming Hormone Therapy (GAHT) Interactions in TGW

A Phase I Trial for the Evaluation of the Two-way Pharmacokinetic-pharmacodynamic (PD) Interaction of Gender Affirming Exogenous Estrogen (With Testosterone Suppression) on TDF/FTC PrEP in Transgender Women (TGW)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This is a research study to determine the best way to dose Truvada®, an oral medication licensed to be taken as Pre-Exposure Prophylaxis (PrEP) to prevent HIV infection, in transgender women who are also taking feminizing hormones. The duration of the study is about 4 months, and involves a screening visit, a baseline visit with colon biopsies and kidney function testing, and several outpatient visits, including 5 intensive sampling visits that last about 9 hours and involve colon biopsies, kidney function testing and other blood specimen collections. After the baseline visit, participants will start on PrEP, daily Truvada® pills, and will continue on the Truvada® for 5 weeks. Participants will then receive either an injection of Lupron, oral low-dose estradiol or oral high-dose estradiol, which will be taken along with the Truvada® PrEP for 1-2 weeks before returning for an intensive sampling visit.

Detailed description

The PrEP-GAHT Interactions in TGW protocol is a phase 1, open label study to compare the safety, PK and PD of five sequential phases of PrEP administration in the presence or absence of testosterone-reducing therapies or dose-escalated estrogen therapy. Each participant will undergo a Screening Visit to evaluate eligibility. Following Baseline evaluation, eligible participants will receive 300 milligrams (mg) TDF/200 mg FTC (Truvada®) once daily for seven days, using direct observation approaches, to achieve steady state drug PrEP concentrations. After one week of therapy, participants will undergo intensive PK analysis as well as collection of colorectal biopsies for PD testing (PK1). During the PK-intensive day, iohexol will be administered intravenously for the empirical determination of renal function and measured glomerular filtration rate (mGFR). While concurrently on PrEP, participants will then be intramuscularly administered depot leuprolide acetate (11.25 mg Lupron®). Two weeks post-injection, when testosterone concentrations are far below the lower limit of normal of total testosterone in men (typically \< 200 ng/dL, or \< 2 ng/mL), sampling for PK, PD, and renal function will be performed (PK2). Participants will then immediately begin low-dose oral estrogen therapy (1 mg 17β-estradiol) in conjunction with PrEP for one week, at which time samples will be collected for the analyses described above (PK3). While still on PrEP, participants will then transition to high-dose estrogen therapy (6 mg 17β-estradiol) for the remainder of the study. One week post-high dose estrogen therapy in the presence of PrEP, pharmacologic and renal samples will be collected for analysis (PK4). PrEP will then be discontinued, and two weeks later, samples will be collected to assess renal function and hormonal concentrations, and evaluate the presence of any remaining PrEP in plasma, Peripheral Blood Mononuclear Cells (PBMC), or colorectal tissue (though it should be near undetectable levels for most analytes according to the investigators' prior data)(PK5). Safety assessments, including history/physical, chemistry/hematology labs at screening and interim history will be performed at each study-intensive visit. Additionally, periodic assessments of gender dysphoria will be conducted at baseline and a convenient time during PK visits throughout the study. To ensure compliance, participants will undergo direct observation of dosing each day of the week prior to PK visits, using the aforementioned strategies.

Conditions

• HIV
• Prophylaxis
• Transgender

Interventions

Type	Name	Description
DRUG	Truvada alone	TDF/FTC 300 mg (milligrams) / 200 mg by mouth once daily
DRUG	Truvada plus Leuprolide 11.25mg intramuscular injection	TDF/FTC 300mg/ 200 mg by mouth once daily Leuprolide 11.25 mg intramuscular injection once
DRUG	Truvada plus Estradiol 1 mg	TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 1 mg by mouth once daily
DRUG	Truvada plus Estradiol 6 mg	TDF/FTC 300mg/ 200 mg by mouth once daily Estradiol 3 mg by mouth twice daily
DRUG	Estradiol 6 mg alone	Estradiol 3 mg by mouth twice daily

Timeline

• Start date: 2021-03-01
• Primary completion: 2025-03-24
• Completion: 2025-03-24
• First posted: 2021-02-18
• Last updated: 2026-04-06
• Results posted: 2026-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study