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Emtricitabine/Tenofovir Alafenamide Switch Study for Transgender Individuals for HIV Pre-exposure Prophylaxis (TAF4TRANS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04616963
Recruitment Status : Recruiting
First Posted : November 5, 2020
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
Sheldon Morris, University of California, San Diego

Brief Summary:
The purpose of this study is to evaluate Pre-Exposure Prophylaxis (PrEP) levels in transgender-identifying or gender non-binary individuals taking versus not taking gender affirming hormone therapy. Subjects who have previously taken F/TDF as PrEP will continue with a fixed dose combination of daily oral F/TAF substituting for F/TDF. Subjects will receive the iTAB text messaging adherence reminders to provide personalized, automated text messages to support and monitor adherence that will vary by participant choice until 12 weeks after switching medication. This study will enroll 60 individuals to take F/TAF as PrEP for 48 weeks.

Condition or disease Intervention/treatment Phase
Hiv Hormone Therapy Drug: Emtricitabine / Tenofovir Disoproxil Oral Tablet 200/300 mg Drug: Emtricitabine Tenofovir Alafenamide 200/25 mg Phase 4

Detailed Description:

This is a two-phased prospective switch study of 60 transgender individuals who are eligible for Truvada® (Emtricitabine/Tenofovir Disoproxil Fumarate) F/TDF PrEP and who are willing to switch to Descovy® (Emtricitabine/Tenofovir Alafenamide) F/TAF for 48 weeks. The purpose of the current study is to contribute safety and efficacy data to support the use of F/TAF in transgender/non-binary individuals. The current study leverages existing studies in trans/non-binary populations (e.g. CCTG 603; HRPP#161807) funded by the California HIV/AIDS Research Program (CHRP).

The dosage for Phase I is FTC 200 mg / TDF 300 mg. The dosage for Phase II is FTC 200 mg / TAF 25 mg. TDF/FTC is FDA approved for use as PrEP in adults and adolescents at risk for HIV-1. F/TAF has received approval by the FDA for use as PrEP as of October 3rd, 2019 except for those having receptive vaginal sex. The FDA has yet to approve F/TAF for use in those having receptive vaginal sex due to a lack of clinical research studies specific to the population. Participants will be advised that if they decide to have receptive vaginal sex while taking F/TAF, they should use another method of protection such as condoms.Eligibility criteria will be based on the CDC guidance for PrEP use in transgender persons. All participants must be confirmed HIV-negative (either by rapid test or Ag/Ab test), must have acceptable safety laboratory values, and must currently be taking or will initiate F/TDF by the Screening/Baseline visit. Participants will have a 12-week lead-in period prior to switching to F/TAF. At the Switch Visit, participants will be instructed to substitute F/TDF with F/TAF for PrEP for 48 weeks. Regular follow-up evaluations will occur at Weeks 12, 24, 36, and 48.

Participants will receive health education, clinical assessments, laboratory safety monitoring, STI and HIV screening, standard HIV risk reduction and adherence counseling, assessment of psychosocial barriers, and completion of a computer-based self-report survey that includes assessments of adherence and risk behaviors. Intracellular TFV-DP quantification will be performed in retrospect on batched, banked samples and additional banked specimens will be frozen for future use. Adherence by TFV-DP concentrations and self-reported measures will be used for the primary and secondary analyses of the study. Additional outcomes for the study will include changes in risk behavior and determinants of PrEP adherence.

This study will continue iTAB, a daily text message support system for adherence up until 12 weeks after F/TAF switch. As needed, the study will provide a) subject reimbursement to pay for unlimited text messaging and/or b) an appropriate cell phone if a subject does not have one. Daily dosing text message reminders will be sent for the duration of the study. Both reminder timing and content can be individualized. Participants have selected 15 personal reminders from a list of pre-determined reminders that cover various themes shown to be effective in improving adherence (e.g., social support, loss frame, health gain, etc.) as developed through focus groups and targeted group feedback. These messages can be modified and the patient can choose to create their own reminders if they prefer. These reminder times can vary for different days of the week to accommodate for changes in schedule (e.g., 8 M-F, and 10 AM on Sat/Sun). Once the time is identified, the text reminder system is automated. Patients will confirm medication taking via text responses to the personalized reminders.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Following Phase I lead-in, all participants will continue PrEP with fixed dose combination daily oral F/TAF substituting for F/TDF in Phase II. Participants will continue to receive PrEP in accordance with standardized comprehensive methods of prescribing, which includes risk reduction counseling, adherence counseling, and clinical assessments with safety monitoring, as well as HIV and STI screening. Participants will receive daily adherence-supporting text message reminders through 12 weeks after F/TAF initiation.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: F/TAF Switch Study for Transgender Individuals for HIV Pre-exposure Prophylaxis (TAF4TRANS)
Actual Study Start Date : October 24, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
FTC 200 mg / TDF 300 mg and FTC 200 mg / TAF 25 mg

Phase I: Participants will continue or initiate F/TDF for PrEP for a minimum 12-week lead-in period prior to switching to F/TAF.

Phase II: Participants will be switched to study-provided F/TAF for PrEP until 48 weeks after initiation. Participants will receive study treatment for the duration of the study unless they meet criteria for discontinuation.

Drug: Emtricitabine / Tenofovir Disoproxil Oral Tablet 200/300 mg
Following Phase I lead-in, all participants will continue PrEP with fixed dose combination daily oral F/TAF substituting for F/TDF in Phase II. Participants will continue to receive PrEP in accordance with standardized comprehensive methods of prescribing, which includes risk reduction counseling, adherence counseling, and clinical assessments with safety monitoring, as well as HIV and STI screening. Participants will receive daily adherence-supporting text message reminders through 12 weeks after F/TAF initiation.
Other Name: Truvada 200Mg-300Mg Tablet

Drug: Emtricitabine Tenofovir Alafenamide 200/25 mg
Following Phase I lead-in, all participants will continue PrEP with fixed dose combination daily oral F/TAF substituting for F/TDF in Phase II. Participants will continue to receive PrEP in accordance with standardized comprehensive methods of prescribing, which includes risk reduction counseling, adherence counseling, and clinical assessments with safety monitoring, as well as HIV and STI screening. Participants will receive daily adherence-supporting text message reminders through 12 weeks after F/TAF initiation
Other Name: Descovy 200Mg-25Mg Tablet




Primary Outcome Measures :
  1. Measuring tenofovir diphosphate (TFV-DP) concentrations [ Time Frame: Baseline-48 weeks ]
    Analysis will be performed on the primary outcome of TFV-DP levels by HT status. Comparison of those on and off HT will be done be t-test. Additional sub-analysis of the primary will stratify by HT type and using both concentrations of TFV-DP and estradiol levels test for correlation. Also cut offs for adherence consistent with 4 doses a week and 7 doses a week will be compared between strata.


Secondary Outcome Measures :
  1. Evaluating safety of F/TAF in transgender individuals compared to F/TDF: adverse events [ Time Frame: Baseline-48 weeks ]
    Safety data will be reported for all participants during use of study drug and immediately after (30 days) completion (as treated analysis). Tables will summarize the number of serious adverse events, adverse events (Grade 1 or higher) over 48 weeks, and PrEP discontinuation due to adverse events.

  2. Evaluating tolerability of F/TAF in transgender individuals compared to F/TDF. [ Time Frame: Baseline-48 weeks ]
    Tolerability will be assessed using Likert scales for those that found favorable tolerability and greater between week 12 F/TDF and week 12 F/TAF.

  3. Adherence to F/TAF in transgender individuals compared to F/TDF [ Time Frame: Baseline-48 weeks ]
    Adherence will be assessed by comparing TFV-DP concentrations commensurate with i) 7 doses/week and ii) 4 doses/week; iii) TFV-DP levels as a continuous measure; and iv) self-reported adherence by text message over 48 weeks between participants on F/TDF versus participants on F/TAF

  4. Evaluating serum creatinine between F/TDF and F/TAF. [ Time Frame: Week 12 ]
    Serum creatinine concentrations will be compared between Week 12 of F/TDF and Week 12 on F/TAF.

  5. Evaluating calculated creatinine clearance between F/TDF and F/TAF. [ Time Frame: Week 12 ]
    Calculated creatinine clearance will be compared between Week 12 of F/TDF and Week 12 on F/TAF.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Transgender or non-binary, defined as identifying with a gender differently from sex assigned at birth
  2. Age 18 years or older
  3. Currently eligible to take F/TDF for PrEP and willing to switch to F/TAF
  4. Negative for HIV infection
  5. Acceptable renal function as measured by calculated creatinine clearance of at least 60 mL/min by the Cockcroft-Gault formula in the past 30 days

Exclusion Criteria:

  1. Unable to give informed consent
  2. Active hepatitis B defined by a positive hepatitis B surface antigen (HBsAg)
  3. Substantial medical condition that, in the opinion of the investigator, would preclude participation, as defined by

    • gastrointestinal condition that would impair absorption of study drugs
    • known condition of reduced bone density (e.g. osteoporosis or osteogenesis imperfect) that significantly elevate the risk of bone fracture
    • neurological or severe psychiatric condition that would significantly impair the ability to adhere to PrEP
    • tubular or glomerular kidney disease that could be exacerbated by tenofovir
    • other medical condition that would unacceptably increase the risk of harm from study drug or significantly impair the ability to adhere to PrEP
  4. Suspected sensitivity or allergy to the study drug or any of its components
  5. Currently using an essential product or medication that interacts with the study drug such as the following:

    • other antiretroviral agent other than F/TDF (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors or investigational antiretroviral agents)
    • agents with known nephrotoxic potential:

      • aminoglycoside antibiotics (including gentamicin)
      • IV amphotericin B
      • cidofovir
      • cisplatin
      • foscarnet
      • IV pentamidine
      • IV vancomycin
      • oral or IV gancyclovir
      • other agents with significant nephrotoxic potential

        - drugs that slow renal excretion

      • probenecid

        - immune system modulators

      • systemic chemotherapeutic agents (i.e. cancer treatment medications)
      • ongoing systemic corticosteroids (with the exception of short courses of tapering steroid doses for asthma or other self- limited condition).
      • interleukin-2 (IL-2)
      • interferon (alpha, beta, or gamma)

        - other agent known to have a significant interaction with TDF, TAF, or FTC

      • the following table includes medications/herbal supplements to be excluded or should be used with caution while participants are taking study drugs due to potential drug-drug interactions with F/TAF.
  6. Proteinuria 2+ or greater by urine dipstick
  7. Pregnancy (if applicable)
  8. Other condition that, in the opinion of the investigator, would put the participant at risk, complicate interpretation of study outcome data, or would otherwise interfere with participation or achieving the study objectives

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04616963


Contacts
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Contact: Leah Burke 619-543-8207 lbburke@health.ucsd.edu
Contact: Helene Le 619-543-3116 helenetle@gmail.com

Locations
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United States, California
UC San Diego AntiViral Research Center (AVRC) Recruiting
San Diego, California, United States, 92103
Contact: Leah Burke    619-543-8207    lbburke@health.ucsd.edu   
Contact: Helene Le    619-543-3116    helenele@health.ucsd.edu   
Principal Investigator: Sheldon Morris, MD, MPH         
Sponsors and Collaborators
University of California, San Diego
Investigators
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Principal Investigator: Sheldon Morris, MD UC San Diego AntiViral Research Center (AVRC)
  Study Documents (Full-Text)

Documents provided by Sheldon Morris, University of California, San Diego:
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Responsible Party: Sheldon Morris, Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04616963    
Other Study ID Numbers: CCTG 605
First Posted: November 5, 2020    Key Record Dates
Last Update Posted: November 5, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sheldon Morris, University of California, San Diego:
Pre-exposure Prophylaxis
PrEP
Hormone Therapy
HT
Additional relevant MeSH terms:
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Tenofovir
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents