Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy

NCT06005610 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: A540338806
• Study Type: interventional
• Target: 93
• Locations: 4 countries
• Sites: 18

Brief Summary

Transgender women (TW) are a key population and priority for HIV treatment. More research is needed to develop evidence-based clinical guidance when it comes to choosing antiretroviral treatment (ART) regimens for TW on feminizing hormonal therapy (FHT). Concerns about ART interacting with FHT and decreasing its effectiveness can lead to decreased ART adherence and increased viral loads. Prior data suggest that access to FHT improves adherence to HIV treatment and decreases treatment interruptions. The Giving Standardized Estradiol Therapy In Transgender Women to Research Interactions with HIV Therapy (GET IT RiGHT) trial aimed to address concerns about drug-drug interactions (DDIs) between ART and FHT while providing access to hormonal therapy to TW living with HIV. This was an open-label, non-randomized, 3-group trial of adult TW and other individuals identifying as female or transfeminine but with male sex assigned at birth living with HIV. Participants were on ART at entry and received study-supplied 17-β estradiol for FHT for up to 48 weeks. The primary objectives of the study were to 1) assess whether TW continue to achieve therapeutic concentrations of ART while receiving FHT for 48 weeks and 2) assess whether serum estradiol concentrations on FHT (across a range of estradiol doses) vary between boosted and un-boosted ART regimens.

Conditions

HIV I Infection

Keywords

HIV; Transgender women; Estradiol; ART; Drug interactions

Outcome Measures

Primary Outcomes (3)

• Geometric Ratio of Antiretroviral Treatment (ART) Analytes Bictegravir (BIC), Dolutegravir (DTG), and Darunavir (DRV) Trough Concentrations (Ctrough) in Plasma at Each Received Dose of Oral 17-β Estradiol

  Log-transformed trough concentrations (Ctrough) in ng/mL of the analytes BIC, DTG, and DRV from plasma samples collected 22-26 hours post ART dose, measured over 48 weeks. Geometric ratios will be calculated as the log of Ctrough of the ART analyte at each dose of 17-β estradiol - log of Ctrough of that same ART analyte at baseline. If multiple observations are available at the same estradiol dose, the first sampled qualifying steady-state trough concentration (based on calendar time) taken will be used.

  Study Entry and Weeks 4, 12, 24, 36, and 48

• Percentage of Participants With ART Analyte Trough Concentration (Ctrough) Above Drug-specific Threshold

  Trough concentration of the analytes BIC, DTG, and DRV in plasma at each received dose of 17-β estradiol summarized at the participant level as indicator of concentration being above drug-specific threshold.

  Study Entry and Weeks 4, 12, 24, 36, and 48

• Trough Serum Total Estradiol Assessed at Each Received Dose of Oral 17-β Estradiol as Quantified Via Batch Testing at Central Lab.

  Trough concentrations of Total 17-β estradiol in ng/mL from serum samples collected 22-26 hours post 17-β estradiol dose. Results \< Lower Limit of Quantification (LLoQ) at entry will be imputed as 0 ng/mL at one-half the LLoQ value at visits post-entry. If multiple observations are available at the same estradiol dose, the first qualifying trough concentration (based on time since last dose) taken will be used.

  Study Entry and Weeks 4, 12, 24, 36, and 48

Secondary Outcomes (24)

• Geometric Ratio of Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) in Non-viable Peripheral Blood Mononuclear Cells (PBMCs) at Each Received Dose of Oral 17-β Estradiol

  Study Entry and Weeks 4, 12, 24, 36 and 48

• Percentage of Participants With Tenofovir Diphosphate (TFV-DP), Emtricitabine Triphosphate (FTC-TP), and Lamivudine Triphosphate (3TC-TP) Trough Concentration Above Drug-specific Threshold

  Study Entry and Weeks 4, 12, 24, 36 and 48

• Percentage of Participants With an Occurrence of Any Reportable Adverse Event Related to 17-β Estradiol

  Treatment initiation to Week 48

• Percentage of Participants With an Occurrence of Any Targeted Adverse Event

  Treatment initiation to Week 48

• Percentage of Participants With Serum Total Testosterone < 50 ng/dL at Each Received Dose of Oral 17-β Estradiol

  Study entry to week 48

Study Arms (3)

Group 1: Estradiol among BIC-treated

EXPERIMENTAL

Participants taking bictegravir (BIC) + tenofovir alafenamide (TAF) + emtricitabine (FTC) who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg.

Drug: Estradiol

Group 2: Estradiol among DTG-treated

EXPERIMENTAL

Participants taking dolutegravir (DTG) once daily + tenofovir disoproxil fumarate (TDF) + (FTC or lamivudine \[3TC\]), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg.

Drug: Estradiol

Group 3: Estradiol among DRV/c-treated

EXPERIMENTAL

Participants taking any anti-retroviral treatment regimen containing darunavir plus cobicistat (DRV/c), who initiated oral 17-β estradiol once daily for 48 weeks starting at 2mg.

Drug: Estradiol

Interventions

Estradiol DRUG

Oral 17-β estradiol 2 mg once daily initiated immediately following entry. At weeks 4, 12, 24, and 36, study clinicians may have titrated 17-β estradiol in 2 mg increments to achieve the desired participant goals and target hormone concentrations, as measured locally at each visit.

Group 1: Estradiol among BIC-treated; Group 2: Estradiol among DTG-treated; Group 3: Estradiol among DRV/c-treated

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Assigned male sex at birth and identifies as a TW, female or transfeminine person.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of HIV-1 status.
• On ART for at least 24 weeks prior to study entry. Regimen changes within the 24 weeks prior to study entry are acceptable, but candidates must have been on a stable regimen for at least 28 days prior to study entry.
• On BIC/FTC/TAF, DTG/TDF/FTC or 3TC, or DRV/c-containing ART for at least 28 days prior to study entry (single tablet regimen not required), and with no plans to change ART regimen over the study duration of 48 weeks.
• Desire to initiate or restart FHT, regardless of orchiectomy status.
• HIV-1 RNA \<200 copies/mL at screening.
• HIV-1 RNA \<400 copies/mL available through routine clinical care between 24 and 96 weeks prior to study entry and while on ART. The HIV-1 RNA must be the most recent value obtained between 24 and 96 weeks prior to study entry.
• The following laboratory values obtained within 60 days prior to study entry
• Hemoglobin ≥9.0 g/dL
• Platelet count ≥75,000/mm3
• Estimated Glomerular Filtration Rate (eGFR) ≥30 mL/min/1.73m2 if on or switching to TAF, ≥50 mL/min/1.73m2 if on or switching to TDF without cobicistat, or ≥70 mL/min/1.73m2 if on or switching to TDF in combination with cobicistat, calculated using standardized equation for eGFR
• Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase are within normal range per local laboratory range
• Prolactin \<25 ng/dL
• Serum estradiol level \<75 pg/mL within 60 days prior to study entry.
• Willingness to avoid the use of prescribed, non-study provided FHT and non-prescribed FHT during the study period, and no planned use of prescribed or non-prescribed anti-androgens for the first 24 weeks of the study.
• Ability and willingness of participant to provide informed consent and ability and willingness of participant to undergo study procedures.

You may not qualify if:

• Known clotting disorders, active deep vein thrombosis (DVT), pulmonary embolism (PE), or history of these conditions, active arterial thromboembolic disease (e.g., stroke, myocardial infarction), or history of these conditions.
• Known liver impairment or disease.
• History of chronic hepatitis B virus (HBV) infection or active HBV infection.
• History of current active hepatitis C virus (HCV) infection.
• Prohibited medication use (including drugs with known or expected DDIs with FHT or ART) at time of study entry.
• Receipt of any estrogen therapy within 14 days prior to study entry for persons on oral FHT, or within 30 days prior to entry for persons on injectable FHT.
• Known HIV-1 resistance mutations that would preclude remaining on current ART or a switch to a study regimen, in the opinion of the site investigator.
• Personal history of breast cancer. or known personal history of breast cancer (BRCA) gene.
• Known or a history of testicular cancer.
• Known or a history of gall bladder disease.
• Known or suspected pituitary adenoma.
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
• Suicidal ideation in the past 30 days or suicide attempt in the past 90 days, as reported on the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry. Stable (in the opinion of the site investigator) treatments for chronic comorbidities are allowed.
• Presence of any other medical condition that would preclude FHT administration for safety reasons, in the opinion of the site investigator.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (18)

UCSD Antiviral Research Center CRS (701)

San Diego, California, 92103, United States

Location

University of California, San Francisco HIV/AIDS CRS (801)

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Whitman-Walker Institute, Inc. CRS (31791)

Washington D.C., District of Columbia, 20005, United States

Location

The Ponce de Leon Center CRS (5802)

Atlanta, Georgia, 30308, United States

Location

Johns Hopkins University CRS (201)

Baltimore, Maryland, 21205, United States

Location

Washington University Therapeutics (WT) CRS (2101)

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS (31786)

Newark, New Jersey, 07103, United States

Location

Weill Cornell Uptown CRS (site 7803)

New York, New York, 10065, United States

Location

Chapel Hill CRS (3201)

Chapel Hill, North Carolina, 27599-7215, United States

Location

Greensboro CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS (31473)

Houston, Texas, 77030, United States

Location

Nutrición-Mexico CRS (32078)

Mexico City, Tlalpan, 14080, Mexico

Location

Barranco CRS (11301)

Lima, 4, Peru

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (31802)

Bangkok, Patumwan, 10330, Thailand

Location

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (31784)

Chiang Mai, 50200, Thailand

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1 - July 20, 2017

MeSH Terms

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Trial was terminated by the sponsor before some participants completed follow-up. Additionally, funding from sponsor unavailable to conduct planned batched testing of stored samples required to generate data for primary and a number of secondary outcomes.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Jordan E. Lake, MD, MSc

  Houston AIDS Research Team CRS

  STUDY CHAIR

• Kimberly K. Scarsi, PharmD, MS, FCCP

  University of Nebraska

  STUDY CHAIR

• Jorge A. Gallardo-Cartagena, MD

  Barranco CRS

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: August 22, 2023
• Study Start: January 4, 2024
• Primary Completion: August 21, 2025
• Study Completion: August 21, 2025
• Last Updated: April 8, 2026
• Results First Posted: April 8, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally(ACTG) by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? To achieve aims in the proposal approved by the ACTG. * By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

PE (1); US (14); ME (1); TH (2)