Evaluating the Safety and Pharmacokinetics of PC-1005 Administered Rectally to HIV-1 Seronegative Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: PC-1005 gel
Intervention description: PC-1005 (0.002% MIV-150/0.3% zinc acetate in 3.0% carrageenan gel) in 4 mL, 16 mL, and 32 mL doses administered rectally.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Microbicides

Summary:

      The purpose of this study is to evaluate the safety and pharmacokinetics of PC-1005 gel when
      used as a rectal microbicide in HIV-uninfected men and women (cis or transgender) with a
      history of consensual receptive anal intercourse.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women (cis or transgender) who are 18 years or older 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 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

          -  At Screening, history of consensual receptive anal intercourse (RAI) at least once in
             their lifetime per participant report

          -  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 follow abstinence requirements for the duration of study participation (See
             the protocol for additional information)

          -  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 and intending to use an effective method
             for the duration of study participation; these include:

               -  Hormonal methods, excluding vaginal rings

               -  Intrauterine device (IUD) inserted at least 42 days prior to Enrollment (but not
                  past the maximum length of recommended usage according to package instructions)

               -  Sterilization of participant or partner at least 42 days prior to Enrollment

               -  Self-identifies as having sex with women exclusively

        Exclusion Criteria:

          -  At Screening:

               -  Hemoglobin Grade 1 or higher*

               -  Platelet count Grade 1 or higher*

               -  White blood count Grade 2 or higher*

               -  Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher*

               -  Serum creatinine greater than 1.3x the site laboratory upper limit of normal
                  (ULN)

               -  International normalized ratio (INR) greater than 1.5x the site laboratory ULN

               -  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 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.

          -  Known adverse reaction to latex or polyurethane (ever)

          -  Anticipated use of and/or unwillingness to abstain from the following medications
             during study participation:

               -  Anticoagulant medications

               -  Rectally-administered medications

          -  Known adverse reaction to any of the components of the study product

          -  Use of pre-exposure prophylaxis (PrEP) for HIV prevention within 1 month 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 the 3 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

          -  Non-therapeutic injection drug use 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

          -  Gynecologic, genital, or rectal procedure (e.g., tubal ligation, dilation and
             curettage, piercing, hemorrhoidal resection, polyp removal) 60 days or less prior to
             Enrollment, or rectal biopsy, 7 days or less prior to Enrollment. Note: Colposcopy and
             cervical biopsies for evaluation of an abnormal Pap test as well as IUD
             insertion/removal are not exclusionary. Anoscopy and endoscopy without rectal biopsies
             are not exclusionary

          -  Per participant report, medical records, clinical diagnosis and/or diagnostic testing
             at either Screening or Enrollment:

               -  Diagnosis or treatment of any anogenital sexually transmitted infection (STI) in
                  the past 3 months (including window between Screening and Enrollment)

               -  Symptoms, clinical or laboratory diagnosis of active pharyngeal, anorectal
                  infection 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,
                  anogenital sores or ulcers, or symptomatic genital warts, chancroid, pelvic
                  inflammatory disease (PID), symptomatic bacterial vaginosis (BV), symptomatic
                  vaginal candidiasis, other vaginitis, and trichomoniasis.

               -  Note: Otherwise eligible participants with an exclusionary UTI, BV and/or candida
                  finding may be re-tested during the screening process.

               -  Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted
                  since treatment is not required.

          -  Participants who meet any of the following additional criteria will be excluded from
             the study:

               -  Pregnant or breastfeeding at either Screening or Enrollment or planning to become
                  pregnant or begin 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 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.