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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
128
dapivirine gel 4789, 0.05%, 2.5g applied once daily
dapivirine gel 4759, 0.05%, 2.5g applied once daily
HEC-based universal placebo gel, 2.5g applied once daily
University of Alabama at Birmingham, Alabama Microbicide Clinical Research Site (AMCRS)
Birmingham, Alabama, United States
Harbor-UCLA Medical Center
Torrance, California, United States
University of Illinois at Chicago
Chicago, Illinois, United States
SNBL Clinical Pharmacology Center
Baltimore, Maryland, United States
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death
Time frame: 12 weeks
Changes in the Vaginal Flora
Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10).
Time frame: 16 weeks
The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point
Dapivirine levels observed in plasma will be summarized using simple descriptive statistics.
Time frame: 12 weeks
The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports.
Time frame: 12 weeks
Changes in the Vaginal pH
Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g.
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Albert Einstein College of Medicine
New York, New York, United States
Time frame: 12 weeks
The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.
The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial.
Time frame: 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).
The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.
The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics.
Time frame: 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).
Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV.
Time frame: 12 weeks