Study of UC-781 Vaginal Microbicide

Study Overview
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Brief Summary
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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
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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

Official Title
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Phase I Study of the Safety and Acceptability of UC-781 Topical Vaginal Microbicide in Heterosexual Women and Their Male Partners

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: topical vaginal application of UC-781 gel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>0.25% gel | Drug: topical vaginal application of UC-781 gel<br>* UC-781 gel (arms 1 and 2) or placebo (arm 3) applied vaginally twice daily for 14 days<br>|
| Active Comparator: 2<br>0.1% gel | Drug: topical vaginal application of UC-781 gel<br>* UC-781 gel (arms 1 and 2) or placebo (arm 3) applied vaginally twice daily for 14 days<br>|
| Placebo Comparator: 3<br> | Drug: topical vaginal application of UC-781 gel<br>* UC-781 gel (arms 1 and 2) or placebo (arm 3) applied vaginally twice daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, topical microbicides