Evaluating the Safety and Pharmacokinetics of PC-1005 Administered Rectally to HIV-1 Seronegative Adults

PC-1005 is a multipurpose prevention technology (MPT) microbicide in development that is
active against HIV, HPV, and HSV-2. This study will evaluate the safety and pharmacokinetics
of PC-1005 gel when administered rectally.

The study will enroll HIV-uninfected men and women (cis or transgender) with a history of
consensual receptive anal intercourse. All participants will receive 3 single escalating
doses of rectally administered PC-1005: 4 mL, 16 mL and 32 mL.

The study includes a total of 9 clinic visits and 1 follow-up contact by phone or in person.
Participants will receive doses of PC-1005 at Visits 3, 5, and 7. A 2-to-6 week washout
period will follow each dosing visit. If no adverse events that preclude continuation to the
next dose are identified during this period, participants will receive the next scheduled
dose of PC-1005. Participation in this study will last approximately 3 to 5 months.

Study visits will include physical examinations, throat swabs, behavioral assessments and
interviews, and collection of blood, urine, rectal tissue, and cervical, vaginal, and rectal
fluid.

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.