Clinical trial NCT00799058: A Safety Study of Two Dapivirine (TMC120) Vaginal Gels in the United States
Official title: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE I/II TRIAL TO EVALUATE THE SAFETY OF DAPIVIRINE GEL 4759, 0.05% 2.5g AND DAPIVIRINE GEL 4789, 0.05% 2.5g FORMULATIONS AS COMPARED TO THE VAGINAL HEC-BASED UNIVERSAL PLACEBO GEL, 2.5g IN HEALTHY HIV-NEGATIVE WOMEN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV-1 Infections
Keywords: HIV-1 infections
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-27
Enrollment: 128
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All enrolled participants will apply gel on a daily basis for 12 weeks, with clinical follow-up visits at weeks 2,4,8 and 12 to monitor safety and acceptability, and a final visit 4 weeks post gel discontinuation (Visit 6, week 16) Dapivirine concentration will be measured in blood and vaginal fluid and cervical tissue.
Primary purpose: PREVENTION

Brief summary: A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine Gel 4759, 0.05% 2.5 g and dapivirine Gel 4789, 0.05% 2.5 g formulations as compared to the vaginal HEC-based Universal placebo gel, 2.5 g in healthy HIV-negative women

Detailed description: This was a double-blind, randomized, placebo-controlled trial, to be conducted over 10 months at five research centers in the USA among 180 healthy, sexually active women, to assess the safety and acceptability of dapivirine Gel 4759, 0.05% 2.5 g, and dapivirine Gel 4789, 0.05% 2.5 g, both vaginal microbicides containing dapivirine, compared to the vaginal HEC-based Universal placebo gel, 2.5 g, containing no active ingredient, used once daily for a period of 12 weeks.

Eligibility criteria: Inclusion Criteria:

1. Women 18 to 40 years of age inclusive who can give written informed consent
2. Available for all visits and consent to follow all procedures scheduled for the trial
3. Healthy and self-reported sexually active
4. HIV-negative as determined by an HIV test at time of enrollment
5. Willing to be on a stable form of contraception
6. In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle
7. Upon pelvic/speculum examination and colposcopy at the enrollment visit, the cervix and vagina appear normal as determined by qualified research center staff
8. Asymptomatic for genital infections at the time of enrollment
9. Willing to refrain from use of vaginal products or objects for 14 days prior to enrollment and for the duration of the trial.
10. Documentation of no abnormality on Pap smear within 90 days prior to randomization;
11. Willing to answer acceptability and adherence questionnaires throughout the trial
12. Willing to refrain from participation in any other research trial for the duration of this trial
13. Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures
14. Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit:

    * Vaginal intercourse
    * Oral contact with her genitalia
    * Internal vaginal washing
    * Penetration of the vagina by fingers, sex toys, or any other objects, including medications
15. Willing to abstain from all of the following for 3 days after biopsy procedures:

    * Vaginal intercourse
    * Oral contact with her genitalia
    * Internal vaginal washing
    * Penetration of the vagina by fingers, sex toys, or any other objects, including medications

Exclusion Criteria:

1. Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening
2. Currently breast-feeding, or having breastfed within 3 months prior to screening
3. Receipt of any investigational agent within 60 days prior to screening
4. Previously participated in any HIV vaccine trial
5. Untreated urogenital infections within 2 weeks prior to enrollment
6. Presence of any abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy
7. History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, or urethral obstruction
8. Pap smear result at screening that requires cryotherapy, biopsy or treatment (other than for infection)
9. History of symptomatic or asymptomatic HSV-2
10. Any Grade 2, 3 or 4 hematology, chemistry or urinalysis laboratory abnormality at baseline
11. Unexplained, undiagnosed abnormal bleeding per vagina during or following vaginal intercourse; or urogenital surgery within 90 days prior to enrollment
12. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex
13. Any serious acute, chronic or progressive disease
14. Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives

Primary outcomes:
measure: The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in the Vaginal Flora
timeFrame: 16 weeks
measure: The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point
timeFrame: 12 weeks
measure: The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
timeFrame: 12 weeks
measure: Changes in the Vaginal pH
timeFrame: 12 weeks
measure: The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.
timeFrame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
measure: The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.
timeFrame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
measure: Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Alabama Microbicide Clinical Research Site (AMCRS)
state: Alabama
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Baltimore
country: United States
facility: SNBL Clinical Pharmacology Center
state: Maryland
city: New York
country: United States
facility: Albert Einstein College of Medicine
state: New York
Study officials:
affiliation: International Partnership for Microbicides
name: Dr Annalene Nel
role: STUDY_CHAIR
References: