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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1 Safety and Pharmacokinetic Study of PC-1005 (MIV-150/Zinc Acetate/Carrageenan Gel) Administered Rectally to HIV-1 Seronegative Adults

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: PC-1005 gel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PC-1005<br>All participants will receive 3 single escalating doses of PC-1005 gel during Visits 3, 5, and 7, with a 2-to-6-week washout period between dosing visits. Each participant will be on study for approximately 3 to 5 months. | Drug: PC-1005 gel<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Grade 2 or Higher Adverse Events (AEs) | AEs are defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital [Dated November 2007], Male Genital [Dated November 2007] and Rectal [Clarification Dated May 2012] Grading Tables for Use in Microbicide Studies). | Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant | 
| MIV-150 Concentrations in Plasma | Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points | Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant | 
| MIV-150 Concentrations in Rectal Fluid | Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points | Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant | 
| MIV-150 Concentrations in Rectal Mucosal Tissue Homogenates | Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points | Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Self-report Gel Acceptability - Ease of Use | Response for Overall, how easy or difficult was it to use the gel when applied by clinic staff? at exit self-interview questionnaire. | Through study completion, approximately 3-5 months for each participant | 
| Participant Self-report Gel Acceptability - Feeling When Inserted | Response for Overall, how did it feel to have the gel inside you? at exit self-interview questionnaire. | Through study completion, approximately 3-5 months for each participant | 
| Participant Self-report Gel Acceptability - Problems With Gel Use | Responses for questions related to problem with gel use at exit self-interview questionnaire | Through study completion, approximately 3-5 months for each participant | 
| Participant Self-report Gel Acceptability - Gel Acceptability | Response for questions related to gel acceptability at exit self-interview questionnaire. | Through study completion, approximately 3-5 months for each participant | 
| MIV-150 Concentrations in Vaginal Fluid | Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points | Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbicides