HIV Infections
Conditions
Keywords
HIV, topical microbicides
Brief summary
This study will help determine whether the agent UC-781, formulated as a gel, is safe when applied to the vagina twice daily for 14 days. It will also assess whether women find the gel acceptable to use.
Detailed description
Purpose: To assess the safety and acceptability of vaginal use of 0.1% and 0.25% UC-781 gel in sexually active HIV-uninfected women, and their male partners, and sexually abstinent HIV-infected women Design: Single-center, phase I randomized, double-blind, controlled trial with 14 days of twice-daily product or control gel exposure Study population: Sexually active, HIV-uninfected women at low-risk for HIV and their male partners; sexually-abstinent HIV-infected women; all age 18-45 Size: 36 sexually active HIV-uninfected women and up to 36 of their male partners; 18 sexually abstinent HIV-infected women Treatment regimen: Stage 1: HIV-uninfected, sexually active women and 1 male partner per woman: 12 women assigned to 0.1% UC-781 twice daily x 14 days; 12 women assigned to 0.25% UC-781 twice daily x 14 days; 12 women assigned to control gel twice daily X 14 days. Stage 2: HIV-infected, abstinent women: 12 assigned to 0.25% UC-781 twice daily x 14 days; 6 assigned to control gel twice daily x 14 days Study duration: Participant accrual will take 6 months. Each participant will be followed for 14 days in Stage 1 and 21 days in Stage 2. Total study duration will be 9 months. Study Site: The Hope Clinic of Emory University, Decatur, GA Primary Objectives: * To assess the safety and toxicity of 0.1% UC-781 gel and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually active HIV-uninfected women * To assess the safety and toxicity of 0.25% UC-781 gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually abstinent HIV-infected women Secondary Objectives: * To assess the acceptability of 0.1% and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days among HIV-uninfected, and the acceptability of 0.25% gel similarly administered to HIV-infected women * To assess the effect of study product on vaginal microflora of HIV-uninfected and HIV-infected women * To assess the systemic absorption of 0.1% and 0.25% UC-781 gel when administered intravaginally * To assess HIV viral load in genital secretions in HIV-infected women during 0.25% UC-781 gel use * To assess the genotypic resistance patterns of HIV in genital secretions and peripheral blood in HIV-infected women during 0.25% UC-781 gel use * To assess the acceptability of 0.1% and 0.25% UC-781 gel in male sexual partners of HIV-uninfected women Primary Endpoints: The safety and toxicity of 0.1% UC-781 gel and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days in sexually-active HIV-uninfected women and 0.25% UC-781 gel administered in sexually-abstinent HIV-infected women will be assessed by: * Macroscopic and/or microscopic evidence of vulvar and/or vaginal epithelium damage, including ulceration, abrasion, severe erythema, and/or severe edema * Macroscopic and/or microscopic evidence of cervical mucosal damage including ulceration, abrasion, severe erythema, and/or severe edema * Symptoms of genital irritation, including burning, itching or soreness * Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause Secondary Endpoints: Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected and 0.25% UC-781 gel use by HIV-infected women will be assessed by: * Proportion of participants who at Day 14 visit indicate they would be 'somewhat unlikely' or 'very unlikely' to use 0.1% and 0.25% UC-781 gel during sexual intercourse in the future compared to control gel users * Reported positive aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users * Reported negative aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users
Interventions
DRUGtopical vaginal application of UC-781 gel
UC-781 gel (arms 1 and 2) or placebo (arm 3) applied vaginally twice daily for 14 days
Sponsors
Emory University
Centers for Disease Control and Prevention
CONRAD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
For All Females: * Ages 18-45 years of age * Able to provide written informed consent * Normal Pap smear at screening or documentation of such within six months prior * Regular monthly menses or amenorrhea due to hormonal contraceptive use * Agree to pelvic exam, colposcopy and biopsy (if indicated) per protocol * Able/willing to complete Study Diary * Agree to abstain from sexual intercourse for 48 hours prior to the enrollment visit * Agree to apply assigned study gel as required per protocol * Agree to abstain from the following activities from at least 48 hours prior to enrollment through the Day 14 visit: * Insertion of fingers/objects into the vagina * Receiving oral sex * Receiving anal sex * Using a diaphragm, cervical cap, female condom, or vaginal contraceptive ring * Using vaginal products other than the study gels * Participating in other vaginal microbicide or contraceptive studies Additional Inclusion Criteria for Stage 1: * HIV-uninfected * In a monogamous sexually active relationship with one male partner throughout the study * Report having vaginal intercourse only with that partner at least two times per week * Agree to use study-provided male condoms for each act of vaginal intercourse while taking part in the study * Agree to inform male partner about participation Additional Inclusion Criteria for Stage 2: * HIV-infected * Sexually abstinent or agree to abstain from sexual intercourse while taking part in the study * Under regular medical care for HIV management * CD4+ lymphocyte count \> 200/mm3 for the last 6 months * HIV viral load \> 4.0 log10 copies/ml at screening * Documentation of prior HIV genotype with one or more mutations conferring resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI) * Not currently on antiretrovirals * Willing to provide study staff with access to medical records related to their HIV infection Inclusion Criteria for Male Partners: * Ages 18 years or older * Able to give written informed consent * Male sexual partners of HIV-uninfected women taking part in Stage 1 of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Symptoms of genital irritation, including burning, itching or soreness | With 2 weeks of administration |
| Macroscopic and/or microscopic evidence of cervical, vulvar and/or vaginal epithelial damage, including ulceration, abrasion, severe erythema, and or severe edema. | with two weeks of administration |
| Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause | with 2 weeks of administration |
Secondary
| Measure | Time frame |
|---|---|
| Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected and HIV-infected women | queried after 2 weeks of administation |
Countries
United States
Outcome results
None listed