Safety and Pharmacokinetic Study of Tenofovir Alafenamide (TAF)/Elvitegravir (EVG) Administered Rectally
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: TAF/EVG Insert
Intervention description: TAF/EVG Insert (20/16 mg) administered rectally by study staff
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety and pharmacokinetics of rectal
      administration of a tenofovir alafenamide (TAF)/elvitegravir (EVG) insert at two dose levels
      in HIV-uninfected individuals.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Individuals who are 18 years of age or older at Screening, verified per site standard
             operating procedure (SOP)

          -  Able and willing to provide written informed consent to be screened for and enrolled
             in MTN-039

          -  HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in the study
             protocol and willing to receive HIV test results

          -  Able and willing to provide adequate locator information, as defined in site SOP

          -  Able to communicate in spoken and written English

          -  Available for all visits and able and willing to comply with all study procedural
             requirements

          -  In general good health at Screening and Enrollment, as determined by the site
             Investigator of Record (IoR) or designee

          -  At Screening, history of consensual receptive anal intercourse (RAI) at least once in
             lifetime per participant report

          -  Willing not to take part in other research studies involving drugs, medical devices,
             genital or rectal products, or vaccines for the duration of study participation
             (including the time between Screening and Enrollment)

          -  Willing to comply with abstinence and other protocol requirements as outlined in the
             study protocol

          -  For participants of childbearing potential: a negative pregnancy test at Screening and
             Enrollment

          -  For participants of childbearing potential: Per participant report at Enrollment,
             using an effective method of contraception for at least 30 days (inclusive) prior to
             Enrollment and intending to use an effective method for the duration of study
             participation. Effective methods include:

               -  Hormonal methods

               -  Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not
                  past the maximum length of recommended usage according to package instructions)

               -  Sterilization (of participant or partner, as defined in site SOPs)

               -  Sexually abstinent as defined by abstaining from penile-vaginal intercourse for
                  90 days prior to Enrollment and intending to remain abstinent for the duration of
                  study participation; this includes having sex exclusively with individuals
                  assigned female sex at birth

        Exclusion Criteria:

          -  At Screening:

               -  Hemoglobin Grade 1 or higher*

               -  Platelet count Grade 1 or higher*

               -  Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher*

               -  Serum creatinine greater than 1.3 times the site laboratory upper limit of normal
                  (ULN)

               -  International normalized ratio (INR) greater than 1.5 times the site laboratory
                  ULN

               -  History of inflammatory bowel disease by participant report

               -  Positive hepatitis B surface antigen (HBsAg) test result

               -  *As per the Division of AIDS Table for Grading the Severity of Adult and
                  Pediatric Adverse Events Corrected Version 2.1, July 2017.

               -  Note: Otherwise eligible participants with an exclusionary test result (other
                  than HIV) can be re-tested during the screening process. If a participant is
                  re-tested and a non-exclusionary result is documented within 45 days of providing
                  informed consent for screening, the participant may be enrolled.

          -  Anticipated use of and/or unwillingness to abstain from the following medications
             during study participation:

               -  Anticoagulant medications

               -  Non-study rectally-administered medications and any products containing
                  nonoxynol-9 (N-9)

          -  Known adverse reaction to any of the components of the study product

          -  Use of approved or other investigational pre-exposure prophylaxis (PrEP) for HIV
             prevention within 3 months prior to Enrollment, and/or anticipated use and/or
             unwillingness to abstain from PrEP during trial participation

          -  Use of post-exposure prophylaxis (PEP) for potential HIV exposure within 6 months
             prior to Enrollment

          -  Condomless RAI and/or penile-vaginal intercourse with a partner who is known to be
             HIV-positive or whose status is unknown in the 6 months prior to Enrollment

          -  History of transactional sex in the 12 months prior to Enrollment

          -  Non-therapeutic injection drug use or use of non-therapeutic, non-injection stimulant
             drugs in the 12 months prior to Enrollment

          -  Participation in research studies involving drugs, medical devices, genital or rectal
             products, or vaccines within 30 days of the Enrollment Visit

          -  Per participant report, medical records, clinical diagnosis and/or diagnostic testing
             at either Screening or Enrollment:

               -  Diagnosis or treatment of an anogenital sexually transmitted infection (STI) in
                  the 3 months prior to enrollment (including window between Screening and
                  Enrollment).

               -  Symptoms, clinical or laboratory diagnosis of active pharyngeal, anorectal, or
                  reproductive tract infection (RTI) requiring treatment per current Centers for
                  Disease Control and Prevention (CDC) guidelines
                  (http://www.cdc.gov/std/treatment).

               -  Current symptomatic urinary tract infection (UTI).

                    -  Infections requiring treatment include Neisseria gonorrhea (GC), Chlamydia
                       trachomatis (CT) infection, syphilis, active herpes simplex virus (HSV)
                       lesions, or symptomatic genital warts, chancroid, pelvic inflammatory
                       disease (PID), bacterial vaginosis (BV), symptomatic vaginal candidiasis,
                       and trichomoniasis.

                    -  Note: Otherwise eligible participants with an exclusionary UTI, BV and/or
                       candida finding may be re-tested during the screening process.

          -  For participants of childbearing potential: Pregnant or breastfeeding at either
             Screening or Enrollment or planning to become pregnant during study participation

               -  Note: A documented negative pregnancy test performed by study staff is required
                  for inclusion; however, a self-reported pregnancy is adequate for exclusion from
                  screening/enrollment into the study.

          -  For participants of childbearing potential: Last pregnancy outcome 90 days or less
             prior to Screening

          -  Has any other condition that, in the opinion of the IoR/designee, would preclude
             informed consent, make study participation unsafe, complicate the interpretation of
             study outcome data, or otherwise interfere with achieving the study objectives
             including any significant uncontrolled active or chronic medical condition.