Study of UC-781 Vaginal Microbicide

CONRAD90 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

HIV Infections

Interventions

topical vaginal application of UC-781 gelDRUG

UC-781 gel (arms 1 and 2) or placebo (arm 3) applied vaginally twice daily for 14 days

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 Exclusion Criteria: Exclusion Criteria for All Females: * Are post-menopausal * Have had a hysterectomy * Clinically significant chronic medical condition (other than HIV) that is considered progressive. * History of malignancy, with the exception of basal cell or squamous cell skin cancer * Pregnant or planning to become pregnant in the next three months * Currently breastfeeding * History of sensitivity or allergy to latex or any compound used in this study * Have received antibiotics in the 14 days prior to enrollment * Have used a spermicide or spermicidally lubricated condom within 7 days prior to enrollment * Have been using a hormonal contraceptive method for less than 3 months prior to enrollment * Have participated in other microbicide or contraceptive studies in the past three months * Grade 3 or higher liver, renal or hematology abnormality, as defined by the Table for Grading the Severity of Adult Adverse Events at screening * Have a positive bacterial urine culture * Currently have a clinically detectable genital abnormality (i.e. vulvar, vaginal, cervical and/or perineal ulcer or lesions or abnormal Pap smear) * In the three months prior to enrollment have had any of the following: * An abnormal Pap smear * A pregnancy * An abortion * An intrauterine device (IUD) * Breakthrough menstrual bleeding * Vaginal bleeding during or following vaginal intercourse * Gynecologic surgery * Signs consistent with a sexually transmitted disease (STD) * Signs of genital trauma * Signs of genital tract infection other than asymptomatic bacterial vaginosis (BV) * In the six months prior to enrollment have had any of the following: * History of treatment for or a diagnosis with a new STD * Exchanged sex for money, drugs or gifts * Protected (with condoms) penile-vaginal or penile-anal sexual contact with more than 4 partners * Unprotected (without condoms) penile-vaginal or penile-anal sexual contact with more than 1 partner * A male sexual partner who was diagnosed or treated for an STD (other than HIV) * A male sexual partner who has injected drugs * Are currently using, or in the last year have used intravenous drugs (except for therapeutic use), crack or other recreational drugs * Are currently abusing, or in the last year have abused alcohol. * Any other condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives Additional Exclusion Criteria for Stage 1: * Unprotected (without condoms) or protected (with condoms) penile-vaginal or penile-anal sexual contact with an HIV-infected partner in the past 6 months * Unwilling to use study-provided male condoms while on study Additional Exclusion Criteria for Stage 2: * NNRTI mutations in plasma and/or genital secretions at screening

Locations (1)

Hope Clinic of Emory University

Decatur, Georgia, United States

Outcomes

Primary Outcomes

Macroscopic and/or microscopic evidence of cervical, vulvar and/or vaginal epithelial damage, including ulceration, abrasion, severe erythema, and or severe edema.

Time frame: with two weeks of administration

Symptoms of genital irritation, including burning, itching or soreness

Time frame: With 2 weeks of administration

Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause

Time frame: with 2 weeks of administration

Secondary Outcomes

Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected and HIV-infected women

Time frame: queried after 2 weeks of administation

Data from ClinicalTrials.gov

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