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Phase I Study of Safety and Persistence of UC-781 Vaginal Microbicide

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

UC-781

UC-781 placebo

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring Anti-Infective Agents, Local, Healthy Women, Microbicides, UC-781, Vaginal Gel, HIV Seronegativity

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria for Screening Visit:

HIV uninfected
General good health
Normal Pap smear within 12 months prior to screen or obtained at screening visit
Anatomy that lends itself easily to visualization of the cervix
Sexual abstinence (including vaginal, oral, and rectal) from Visit 1 to the completion of Visit 4
Agree to use condoms provided by the study between Visits 4 and 5
Agree to abstain from the use of intravaginal products or vaginal penetration throughout the study
Willing to use acceptable forms of contraception until the completion of study
Willing to participate in all study-related assessments and follow all study-related procedures

Inclusion Criteria for Study Entry:

Meet all inclusion criteria for the screening visit at Study Entry
Willing to stay in the Magee-Womens Hospital Clinical Research Center (MWH CRC) for up to 9 hours after gel insertion

Exclusion Criteria for Screening Visit:

Menopause (at least 12 months without menses in absence of long-acting progestin use)
Hysterectomy
Latex allergy
Use of a diaphragm, NuvaRing, or spermicide for contraception
Diagnosed urogenital infection or suspected infection 21 days prior to study screening. More information on this criterion can be found in the protocol.
Menses or other vaginal bleeding anticipated in the 17 days postscreening
Antibiotic or antifungal therapy (vaginal or systemic) 14 days prior to study screening
Injected nontherapeutic drugs 12 months prior to study screening
Systemic immunosuppressive drug use 60 days prior to study screening
Participation in drug, spermicide, and/or microbicide study 30 days prior to study screening
Any condition that, in the opinion of the investigator, would interfere with the study
Intravaginal use of any device or product (except tampons) 7 days prior to study screening
Surgical procedure involving the pelvis in the 90 days prior to enrollment (e.g., dilation and curettage or evacuation, cervical biopsy, cryosurgery,any other surgery involving pelvic organs or area)
Abnormal pelvic exam finding that, in the opinion of the investigator would complicate interpretation of the colposcopy
Pregnancy, or within 90 days of last pregnancy
Breastfeeding

Exclusion Criteria for Study Entry:

Meets any of the exclusion criteria of the screening visit
Diagnosed or suspected reproductive tract infection or urinary tract infection. More information on this criterion can be found in the protocol.
Menses or other vaginal bleeding anticipated in the 8 days following study entry
Injected nontherapeutic drugs between study screening and study entry
Certain abnormal laboratory values

Sites / Locations

Magee-Womens Hospital of University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 8 hours

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 8 hours

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 4 hours

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 4 hours

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 2 hours

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 2 hours

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 0 hours

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 0 hours

Outcomes

Primary Outcome Measures

Local and systemic safety of a one-time dose of UC-781 0.1 % gel for vaginal use at different durations of exposure in HIV uninfected women

Secondary Outcome Measures

Persistence of UC-781 0.1% gel following a single application

Systemic absorption of UC-781 following a single application of 0.1% UC-781 gel

In vitro anti-HIV activity of cervicovaginal lavage fluid

Product acceptability

Measurement of vaginal flora characteristics

Changes in vaginal flora characteristics after a timed, single exposure

Full Information

NCT ID

NCT00441909

First Posted

February 27, 2007

Last Updated

March 3, 2009

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

CONRAD

1. Study Identification

Unique Protocol Identification Number

NCT00441909

Brief Title

Phase I Study of Safety and Persistence of UC-781 Vaginal Microbicide

Official Title

Phase I Study of the Safety and Persistence of 0.1% UC-781 Vaginal Gel in HIV-1 Seronegative Women

Study Type

Interventional

2. Study Status

Record Verification Date

March 2009

Overall Recruitment Status

Completed

Study Start Date

April 2006 (undefined)

Primary Completion Date

April 2008 (Actual)

Study Completion Date

April 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

CONRAD

4. Oversight

5. Study Description

Brief Summary

Vaginal microbicides are compounds that may protect women from HIV and other sexually transmitted infections (STIs). This study will determine the safety of the microbicide UC-781 by comparing the effects of keeping the microbicide in the vagina for different lengths of time.

Detailed Description

Vaginal microbicides are compounds applied to the inside of the vagina that may protect women against vaginal transmission of HIV and other STIs. This study will evaluate the safety of the vaginal microbicide UC-781. Studies have shown UC-781 to be an effective inhibitor of HIV-1 reverse transcriptase. UC-781 has been tested in animal models and in Phase I and II studies in humans. The results of these studies indicated that cervical tissue was fully protected from different variants of HIV. The purpose of this study is to assess the incidence of epithelial disruption and inflammation in the cervix, vagina, and vulva of healthy HIV uninfected women after a single exposure to UC-781 vaginal gel. This study will compare the results of leaving the microbicide in the vagina for varying lengths of time. The duration of this study is approximately 35 days. Participants in this study will be randomly assigned to one of eight groups, and all participants will receive a single exposure of UC-781 or placebo gel. There will be five total study visits, including the screening and study entry visits. Screening will occur approximately 10 days prior to the study entry visit. At study entry, a single application of microbicide or placebo gel will be inserted for 0, 2, 4,or 8 hours in the vagina. Length of exposure time will differ, depending on which group a participant has been randomly assigned to. Following vaginal exposure to the microbicide, the microbicide will be rinsed off. Vaginal secretions will be collected to test antiviral activity against HIV and assess the amount of microbicide remaining in the vagina. Visits 3 through 5 occur at approximately 24 to 48 hours, 6 to 8 days, and 25 to 35 days following study entry. At all visits, participants will be asked to complete a questionnaire and undergo a pelvic exam, STI tests, and vital signs measurements. Blood and urine collection will occur at each visit. On selected visits, a colposcopy will be conducted and participants will be interviewed regarding product acceptability, in addition to other measures. Between selected visits, participants will be asked to maintain sexual abstinence or use condoms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Anti-Infective Agents, Local, Healthy Women, Microbicides, UC-781, Vaginal Gel, HIV Seronegativity

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 8 hours

Arm Title

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 8 hours

Arm Title

Arm Type

Experimental

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 4 hours

Arm Title

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 4 hours

Arm Title

Arm Type

Experimental

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 2 hours

Arm Title

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 2 hours

Arm Title

Arm Type

Experimental

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide, which will be inserted for 0 hours

Arm Title

Arm Type

Placebo Comparator

Arm Description

Participants will receive a single application of UC-781 vaginal microbicide placebo, which will be inserted for 0 hours

Intervention Type

Drug

Intervention Name(s)

UC-781

Intervention Description

0.1% UC-781 Vaginal Gel

Intervention Type

Drug

Intervention Name(s)

UC-781 placebo

Intervention Description

Vaginal Gel Placebo

Primary Outcome Measure Information:

Title

Local and systemic safety of a one-time dose of UC-781 0.1 % gel for vaginal use at different durations of exposure in HIV uninfected women

Time Frame

Throughout study

Secondary Outcome Measure Information:

Title

Persistence of UC-781 0.1% gel following a single application

Time Frame

At 0, 2, 4, or 8 hours post application

Title

Systemic absorption of UC-781 following a single application of 0.1% UC-781 gel

Time Frame

At 0, 2, 4, or 8 hours post application

Title

In vitro anti-HIV activity of cervicovaginal lavage fluid

Time Frame

Throughout study

Title

Product acceptability

Time Frame

Throughout study

Title

Measurement of vaginal flora characteristics

Time Frame

Throughout study

Title

Changes in vaginal flora characteristics after a timed, single exposure

Time Frame

Throughout study

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria for Screening Visit: HIV uninfected General good health Normal Pap smear within 12 months prior to screen or obtained at screening visit Anatomy that lends itself easily to visualization of the cervix Sexual abstinence (including vaginal, oral, and rectal) from Visit 1 to the completion of Visit 4 Agree to use condoms provided by the study between Visits 4 and 5 Agree to abstain from the use of intravaginal products or vaginal penetration throughout the study Willing to use acceptable forms of contraception until the completion of study Willing to participate in all study-related assessments and follow all study-related procedures Inclusion Criteria for Study Entry: Meet all inclusion criteria for the screening visit at Study Entry Willing to stay in the Magee-Womens Hospital Clinical Research Center (MWH CRC) for up to 9 hours after gel insertion Exclusion Criteria for Screening Visit: Menopause (at least 12 months without menses in absence of long-acting progestin use) Hysterectomy Latex allergy Use of a diaphragm, NuvaRing, or spermicide for contraception Diagnosed urogenital infection or suspected infection 21 days prior to study screening. More information on this criterion can be found in the protocol. Menses or other vaginal bleeding anticipated in the 17 days postscreening Antibiotic or antifungal therapy (vaginal or systemic) 14 days prior to study screening Injected nontherapeutic drugs 12 months prior to study screening Systemic immunosuppressive drug use 60 days prior to study screening Participation in drug, spermicide, and/or microbicide study 30 days prior to study screening Any condition that, in the opinion of the investigator, would interfere with the study Intravaginal use of any device or product (except tampons) 7 days prior to study screening Surgical procedure involving the pelvis in the 90 days prior to enrollment (e.g., dilation and curettage or evacuation, cervical biopsy, cryosurgery,any other surgery involving pelvic organs or area) Abnormal pelvic exam finding that, in the opinion of the investigator would complicate interpretation of the colposcopy Pregnancy, or within 90 days of last pregnancy Breastfeeding Exclusion Criteria for Study Entry: Meets any of the exclusion criteria of the screening visit Diagnosed or suspected reproductive tract infection or urinary tract infection. More information on this criterion can be found in the protocol. Menses or other vaginal bleeding anticipated in the 8 days following study entry Injected nontherapeutic drugs between study screening and study entry Certain abnormal laboratory values

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sharon L. Hillier, PhD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Harold C. Wiesenfeld, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Magee-Womens Hospital of University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15078894

Citation

Davis CW, Doms RW. HIV transmission: closing all the doors. J Exp Med. 2004 Apr 19;199(8):1037-40. doi: 10.1084/jem.20040426. Epub 2004 Apr 12. No abstract available.

Results Reference

background

PubMed Identifier

15817959

Citation

Joshi S, Solomon S, Mayer K, Mehendale S. Preparing for efficacy trials of vaginal microbicides in Indian women. Indian J Med Res. 2005 Apr;121(4):502-9.

Results Reference

background

PubMed Identifier

15743896

Citation

Keller MJ, Tuyama A, Carlucci MJ, Herold BC. Topical microbicides for the prevention of genital herpes infection. J Antimicrob Chemother. 2005 Apr;55(4):420-3. doi: 10.1093/jac/dki056. Epub 2005 Mar 2.

Results Reference

background

PubMed Identifier

15923284

Citation

Minnis AM, Padian NS. Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions. Sex Transm Infect. 2005 Jun;81(3):193-200. doi: 10.1136/sti.2003.007153.

Results Reference

background

PubMed Identifier

15916473

Citation

Weber J, Desai K, Darbyshire J; Microbicides Development Programme. The development of vaginal microbicides for the prevention of HIV transmission. PLoS Med. 2005 May;2(5):e142. doi: 10.1371/journal.pmed.0020142. Epub 2005 May 31.

Results Reference

background

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Phase I Study of Safety and Persistence of UC-781 Vaginal Microbicide

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