Last updated 7 days ago
Estradiol Therapy In Transgender Women to Research Interactions With HIV Therapy
90 patients around the world
Available in Peru, Brazil, Mexico, United States
A5403 is a phase IIb, 48-week, open-label, non-randomized, 3-group trial, of 90 adult
(≥18 years) transgender women and other individuals identifying as female or
transfeminine but with male sex assigned at birth (TW) living with HIV on suppressive
antiretroviral therapy (ART) and not currently on FHT. The trial will target at least 50%
enrollment of participants identifying as non-white or Latine.
The trial consists of three groups, a BIC-treated group (BIC/TAF/FTC; n=30) (Group 1), a
DTG-treated group (DTG/TDF/FTC or 3TC; n=30) (Group 2), and a boosted DRV-treated group
(DRV/c; n=30) (Group 3), for a total of 90 participants.
All participants will continue on ART (not provided by the trial) and receive
study-supplied 17-β estradiol for weeks 0-48. At entry, participants will be assigned to
one of the three analysis groups based on their current ART regimen. Participants on
other ART regimens at screening who are willing to switch to one of the regimens above,
may also be enrolled.
All participants will receive study supplied 17-β estradiol for weeks 0-48. Oral 17-β
estradiol 2 mg once daily will be initiated at study entry. At weeks 4, 12, 24, and 36,
study clinicians may titrate 17-β estradiol in 2 mg increments as described in the
protocol.
Intensive PK subgroup (n=15 per ART group): At entry (week 0), an 8-hour intensive PK
sampling will assess ART exposure prior to FHT initiation. At week 24, intensive sampling
will be repeated to assess 17-β estradiol and ART exposure. A final intensive PK visit
will occur at week 48 to assess 17-β estradiol and ART exposure at the maximal FHT dosing
achieved during the study period.
Sparse PK sampling: all participants not participating in an intensive PK sampling visit
on the same day will have timed, sparse PK sampling collected at each visit to
characterize the trough plasma (BIC, DTG, and DRV) and intracellular ART (TFV-DP, FTC-TP,
3TC-TP) concentrations to evaluate the relationship of ART PK exposure across a range of
17-β estradiol doses.
FHT satisfaction and acceptability:
To measure acceptability, participants will be asked to self-report the degree to which
they find the intervention appropriate and useful using Likert-type agreement scales at
three study time points: entry, 24 weeks, and 48 weeks. To measure satisfaction, the
12-question Transgender Congruence Scale (TCS) will be used, which will assess
associations between gender-affirming treatments, perceived gender congruence, and
satisfaction at three study time points: entry, 24 weeks, and 48 weeks. In addition,
brief, 20-minute, semi-structured interviews will be conducted with 30 purposively
sampled participants across English- or Spanish-speaking sites to provide an opportunity
for more in-depth (open-ended) feedback on intervention satisfaction and acceptability at
three time points: entry, 24 weeks, and 48 weeks.
Other assessments throughout the study include: anthropometric measurements (including
weight, height, minimum waist circumference, and maximum hip circumference), routine
chemistry and hematology labs, HIV-1 RNA, CD4+ and CD8+ T cell counts and percentages,
lipids, glucose and insulin, non-estradiol hormone concentrations, stored PBMC, plasma,
and serum, and ART and FHT adherence assessments.
National Institute of Allergy and Infectious Diseases (NIAID)
2Research sites
90Patients around the world
This study is for people with
Hiv
Requirements for the patient
From 18 Years
Male
Medical requirements
- Age greater than or equal to 18 years.Documentation of HIV-1 status.Assigned male sex at birth and identifies as a TW, female or transfeminine person.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 the CKD-Epi equation,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.
- 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.
Sites
Hospital Nossa Senhora da Conceição
Asociación Civil Impacta Salud y Educación - Barranco Clinical Research Site
StudyGET IT RIgHT
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Conditions
Hiv
Requirements
From 18 YearsMale
Unique study IDclinicaltrials.gov
NCT06005610
