Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dapivirine gel; Placebo gel
Intervention description: Dapivirine gel (0.05%); administered rectally; Universal HEC placebo gel; administered rectally
Intervention MeSH terms: Dapivirine
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of dapivirine
      gel (0.05%) administered rectally to HIV-1 seronegative adults.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age of 18 - 45 years (inclusive) at Screening, verified per site standard operating
             procedure (SOP)

          -  Able and willing to provide written informed consent

          -  HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix
             II of the protocol and willing to receive HIV test results

          -  Able and willing to provide adequate locator information, as defined in site SOP

          -  Available to return for all study visits and willing to comply with study
             participation requirements

          -  In general good health at Screening and Enrollment, as determined by the site
             Investigator of Record (IoR) or designee

          -  Per participant report, a history of consensual receptive anal intercourse (RAI) at
             least once in the past calendar year

          -  Willing to not 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 be sexually abstinent for 72 hours prior to each study visit, during the
             study product use periods and for 72 hours after biopsy collection. Note: See Criteria
             12 and 13 for additional restrictions for female participants

          -  Willing to abstain from inserting any non-study products into the rectum for 72 hours
             prior to each study visit and during the study product use periods. Note: See Criteria
             12 and 13 for additional restrictions for female participants

        Females must also meet the following additional inclusion criteria to be eligible for study
        inclusion:

          -  Women over the age of 21 (inclusive) must have documentation of a satisfactory Pap
             within the past 3 years prior to Enrollment consistent with Grade 0 according to the
             Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (dated November
             2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected
             Version 2.1, July 2017, or satisfactory evaluation with no treatment required of Grade
             1 or higher Pap result

          -  Willing to be sexually abstinent for 72 hours prior to each study visit and during the
             study product use periods and for 7 days after biopsy collection

          -  Willing to abstain from inserting any non-study products into the vagina for 72 hours
             prior to each study visit, during the study product use periods and for 7 days after
             biopsy collection

          -  Willing to use an effective method of contraception for at least 30 days (inclusive)
             prior to Enrollment and intending to continue use of an effective method for the
             duration of study participation; effective methods include: hormonal methods (except
             contraceptive ring), intrauterine device (IUD), sterilization (of participant and/or
             partner, as defined in site SOPs), or sexually abstinent for 90 days prior to
             Screening

        Exclusion Criteria:

          -  At Screening:

               -  Hemoglobin Grade 1 or higher*

               -  Platelet count Grade 1 or higher*

               -  White blood count Grade 2 or higher*

               -  Serum creatinine greater than 1.3× the site laboratory upper limit of normal
                  (ULN)

               -  International normalized ratio (INR) greater than 1.5× the site laboratory ULN

               -  Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher*

               -  Positive for hepatitis C antibody

               -  Positive for hepatitis B surface antigen

               -  History of inflammatory bowel disease by participant report

               -  *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, HBV or HCV) 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:

               -  Heparin, including Lovenox®

               -  Warfarin

               -  Plavix® (clopidogrel bisulfate)

               -  Aspirin (greater than 81 mg)

               -  Non-steroidal anti-inflammatory drugs (NSAIDS)

               -  Any other drugs that are associated with increased likelihood of bleeding

               -  CYP3A inducer(s) and/or inhibitor(s) as specified in the MTN-026 Study-Specific
                  Procedures (SSP) Manual

               -  Hormone-replacement therapy in tablet, injectable or gel form

          -  Known adverse reaction to any of the components of the study products

          -  Use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 6 months
             prior to Enrollment

          -  Use of pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to
             Enrollment, and/or anticipated use during trial participation

          -  Use of systemic immunomodulatory medications within the 6 months prior to Enrollment,
             and/or anticipated use during trial participation

          -  RAI without a condom and/or penile-vaginal intercourse with a partner who is known to
             be HIV-positive in the past 6 months

          -  Non-therapeutic injection drug use in the 12 months prior to Screening and Enrollment

          -  Participation in research studies involving drugs, medical devices, genital or rectal
             products, or vaccines within 45 days of the Enrollment Visit

          -  At Screening, participant report of treatment for an anogenital STI within the past 3
             months

          -  At Screening, participant-reported symptoms and/or clinical or laboratory diagnosis of
             active anorectal or reproductive tract infection requiring treatment per current World
             Health Organization (WHO) guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or
             symptomatic urinary tract infection (UTI). Infections requiring treatment include
             symptomatic Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) infection, syphilis,
             active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic
             genital warts, cervicitis, chancroid, pelvic inflammatory disease (PID), bacterial
             vaginosis (BV), symptomatic vaginal candidiasis, other vaginitis, trichomoniasis.
             Note: Otherwise eligible participants with an exclusionary UTI, BV and/or candida
             finding may be re-tested during the screening process.

          -  At Enrollment, active anorectal or reproductive tract infection requiring treatment
             per current WHO guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or symptomatic
             urinary tract infection (UTI). Infections requiring treatment include symptomatic GC,
             CT, syphilis, active HSV lesions, anogenital sores or ulcers, symptomatic genital
             warts, bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis,
             trichomoniasis, chancroid, cervicitis and PID. Note: HSV-1 or HSV-2 seropositive
             diagnosis with no active lesions is permitted since treatment is not required

          -  Has any other condition that, in the opinion of the IoR/designee, would preclude
             informed consent, make study participation unsafe, complicate interpretation of study
             outcome data, or otherwise interfere with achieving study objectives.

        Females who meet any of the following additional criteria will be excluded from the study:

          -  Pregnant or breastfeeding at either Screening or Enrollment or intends to become
             pregnant or start breastfeeding 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.

          -  Last pregnancy outcome 90 days or less prior to Screening

          -  Has had a hysterectomy

          -  At Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding
             (observed by study clinician or designee) per the Female Genital Grading Table for Use
             in Microbicide Studies [Addendum 1, Dated November 2007]. Note: Cervical friability
             bleeding associated with speculum insertion and/or specimen collection judged to be
             within the range of normal according to the clinical judgment of the IoR/designee is
             considered expected non-menstrual bleeding and is not exclusionary.