NCT04760691·Phase 1·INTERVENTIONAL

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

Leuprolide Other Completed

Status

Completed

Phase

Phase 1

Enrollment

13

Locations

1

Results

Posted

Publications

0

Study summary

What the protocol is testing.

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.

Full 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.

Interventions

Treatment arms and agents.

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

From registration to results.

First posted
Feb 18, 2021
Study start
Mar 1, 2021
Primary completion
Mar 24, 2025
Study completion
Mar 24, 2025
Results posted
Apr 3, 2026
Registry updated
Apr 6, 2026

Outcomes

What the study measures.

Primary outcomes

Change in Maximum Tenofovir Plasma (Cmax) Concentration

Time frame · Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.

Plasma TFV Cmax was defined as the highest observed concentration during the 24 hour (h) dosing interval and determined via non-compartmental analyses. Median maximum concentrations with interquartile ranges (IQR) were determined. Differences in TFV Cmax concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in TFV Cmax, with IQRs, was calculated.

Change in Calculated Plasma TFV Area Under the Concentration-Time Curve (AUC0-24h)

Time frame · Days 7-8 for Pre-Exposure Prophylaxis (PrEP) Only, Days 21-22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Days 28-29 for PrEP Plus Lose-Dose Estrogen, Days 35-36 for PrEP Plus High-Dose Estrogen, and Days 49-50 for High-Dose Estrogen.

The reported AUC is the area under the curve of the concentration-time curve calculated using trapezoidal rule (sum of trapezoids) over a 24h period (AUC0-24h). Median AUCs and IQRs were determined. Changes in AUC0-24h from baseline were based on comparisons between the reported AUC during each dosing period. Differences in the TFV AUC0-24h were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the TFV AUC0-24h, with IQRs, was calculated.

Change in PBMC TFV-DP C24 Concentration

Time frame · Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen.

The PBMC TFV-DP (fmol/10\^6 cells) concentration was measured at 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median PBMC TFV-DP concentrations, normalized to millions of cells analyzed, were measured. Differences in the PBMC TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the PBMC TFV-DP Concentrations, with IQRs, was calculated.

Change in TFV-DP Colon Tissue Concentration

Time frame · Day 8 for Pre-Exposure Prophylaxis (PrEP) Only, Day 22 For PrEP Plus Gonadotropin Releasing Hormone (GnRH) Agonist, Day 29 for PrEP Plus Lose-Dose Estrogen, Day 36 for PrEP Plus High-Dose Estrogen, and Day 50 for High-Dose Estrogen

The estimated colon TFV-DP was measured from colon biopsies 24 hours following a directly observed F/TDF or high-dose estrogen dose. Median colon tissue TFV-DP concentrations (with IQRs), normalized to weight of tissue biopsy analyzed, were measured. Differences in the colonic tissue TFV-DP concentrations were determined for each participant, and each dosing period was compared to the PrEP Only Dosing Period. The median intra-individual difference in the colonic tissue TFV-DP concentrations, with IQRs, was calculated.