Safety, PK, and PD Study of a Vaginal Insert Containing TAF and EVG
Condition: Hiv; HSV
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this Phase I study is to assess the safety, pharmacokinetics, and
      pharmacodynamics of a combination vaginal insert containing tenofovir alafenamide (TAF) and
      elvitegravir (EVG).

      This study will be the first-in-human study for a vaginally administered TAF/EVG insert and
      will evaluate safety, PK and PD after a single dose. It is hypothesized that the combination
      insert will be safe and well-tolerated by study participants and that the insert will offer
      an expanded window of preventive activity and a regimen with flexibility and forgiveness.
    

Detailed description: 
      This Phase I study aims to complete at least 16 healthy, non-pregnant, HIV-uninfected women
      aged 18-50 years who are not at risk for pregnancy and are at low risk for sexually
      transmitted infections (STIs) at one clinical site. The study will examine the safety, PK,
      PD, disintegration, and acceptability of vaginal inserts containing the combination of
      tenofovir alafenamide (TAF) and elvitegravir (EVG).

      Participants will be randomized (1:1) into one of two sample collection time point groups:

      [Timepoint group 1: 4 and 48 hours after using the single combination insert] or [Timepoint
      group 2: 24 and 72 hours after using the single combination insert]

      There will be 5 scheduled visits:

      Visit 1 (Screening/Enrollment): Volunteers will be consented and undergo tests and procedures
      to confirm they are eligible to continue in the study.

      Visit 2 (Baseline): Once it has been confirmed that participants are eligible and willing to
      continue, they will be asked to complete a short baseline questionnaire about the insert.
      Participants will be randomized to Timepoint group 1 or Timepoint group 2 for sample
      collection and will then undergo baseline sampling [cervicovaginal (CV) fluid and tissue].

      Visit 3 (Insert use and sampling): Participants will use a single combination insert of
      TAF/EVG in the clinic. Depending upon timepoint randomization, percentage disintegration of
      the vaginal inserts will be assessed at either 4 hours or 24 hours, and PK and PD sample
      collection (plasma, CV fluid, and CV tissue) will occur. Participants will also be asked to
      complete a short acceptability questionnaire.

      Visit 4 (Post-Dose Sampling): Participants will undergo sample collection of blood for safety
      and PK evaluations; and CV fluid and CV tissue for PK at either 48 hours or 72 hours
      depending upon timepoint randomization.

      Visit 5 (Post-Dose Sampling): Participants will undergo a PK sample collection (CV fluid) 7
      (±2) days post dose. Participants will be asked about adverse events and concomitant
      medications taken. Participants will then be exited from the study, unless they have symptoms
      that require follow-up.

      There will be 5 scheduled visits over approximately 1-3 months.
    

Intervention name(s): TAF/EVG Vaginal Insert
Intervention type(s): Drug
Intervention description(s): 1 combination vaginal insert (20mg TAF/16mg EVG)
Intervention model: Single Group Assignment
Intervention model description: All participants will use a single combination TAF/EVG vaginal insert.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV; TAF; EVG; Prevention; Vaginal Insert