Study of UC-781 Vaginal Microbicide
- Conditions
- HIV Infections
- Interventions
- Drug: topical vaginal application of UC-781 gel
- Registration Number
- NCT00132444
- Lead Sponsor
- CONRAD
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
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 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
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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
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Are currently using, or in the last year have used intravenous drugs (except for therapeutic use), crack or other recreational drugs
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Are currently abusing, or in the last year have abused alcohol.
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3 topical vaginal application of UC-781 gel - 1 topical vaginal application of UC-781 gel 0.25% gel 2 topical vaginal application of UC-781 gel 0.1% gel
- Primary Outcome Measures
Name Time Method 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 Symptoms of genital irritation, including burning, itching or soreness 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 with 2 weeks of administration
- Secondary Outcome Measures
Name Time Method Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected and HIV-infected women queried after 2 weeks of administation
Trial Locations
- Locations (1)
Hope Clinic of Emory University
🇺🇸Decatur, Georgia, United States