Finding the Right Tenofovir/Emtricitabine Regimen for Pre-Exposure Prophylaxis (PrEP) in Transgender Women

NCT03060785 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00092121
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, steady-state study of Tenofovir (TFV) and Emtricitabine (FTC) pharmacokinetics (PK) in transgender women taking feminizing hormones. Half of the participants will be transgender women on feminizing hormones, the other half will be male volunteers not taking any hormone therapy.

Conditions

HIV Prevention

Outcome Measures

Primary Outcomes (1)

• Colon tissue tenofovir diphosphate (TFV-DP)

  Endoscopy will be performed to obtain colorectal tissue biopsies. 15 biopsies will be collected and processed to isolate mucosal mononuclear cells (MMC). TFV-DP will be measured and reported as femtomoles per million cells (fmole/10E6 cells).

  One week

Secondary Outcomes (1)

• Ex vivo colon explant HIV challenge

  One week

Study Arms (2)

TFV/FTC dosing in Transgender women

EXPERIMENTAL

Single daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada)for 7days in transgender women taking feminizing hormones

Drug: Tenofovir Disoproxil Fumarate/Emtricitabine

TFV/FTC dosing in Cis men

ACTIVE COMPARATOR

Single daily dose of oral Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada) for 7days in cis men

Drug: Tenofovir Disoproxil Fumarate/Emtricitabine

Interventions

Tenofovir Disoproxil Fumarate/Emtricitabine DRUG

Also known as: Truvada

TFV/FTC dosing in Cis men; TFV/FTC dosing in Transgender women

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Transgender women (TGW) Cis men (male at birth and not a TGW)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• TGW and cis men (male at birth and not a TGW)
• to 65 years of age, inclusive on the date of screening
• Provides informed consent for the study
• Non-reactive HIV test results within four weeks of enrollment
• An estimated calculated creatinine clearance (eCcr) of at least 70 mL/min
• Agrees to use condoms for all sexual events during study participation.
• Taking daily oral Truvada® (Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg) for at least one week at the time of study PK sampling visit
• TGW have to be on an estradiol and have a serum total estradiol level \> 100 picograms(pg)/ml

You may not qualify if:

• Significant colorectal symptom(s) as determined by medical history or by participant self-report
• Participant-reported symptoms and/or clinical or laboratory diagnosis of active rectal infection requiring treatment per current Centers for Disease Control (CDC) guidelines
• A positive test for Herpes Simplex Virus -2 (HSV-2) (individuals with active lesions only)
• Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
• Positive hepatitis B surface antigen (HBsAg) test
• Interleukin therapy; medications with significant nephrotoxic potential, including but not limited to amphotericin B, aminoglycosides, cidofovir, foscarnet and systemic chemotherapy; medications that may inhibit or compete for elimination via active renal tubular secretion (including but not limited to probenecid); systemic immunomodulatory medications
• Participants with a history of having a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption
• Medications that prolong clotting time
• Any other condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University Drug Development Unit

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Shieh E, Marzinke MA, Fuchs EJ, Hamlin A, Bakshi R, Aung W, Breakey J, Poteat T, Brown T, Bumpus NN, Hendrix CW. Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men. J Int AIDS Soc. 2019 Nov;22(11):e25405. doi: 10.1002/jia2.25405.

  PMID: 31692269 DERIVED

MeSH Terms

Interventions

Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Craig Hendrix, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: March 8, 2016
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: July 18, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)