MTN-004

Primary Objective

• Assess the safety of VivaGel^® when administered for 14 consecutive days on the vulvar and cervicovaginal mucosa of healthy sexually active HIV-negative women aged 18-24 years

Study Summary
MTN-004 was a two site, Phase 1, double-blind, placebo-controlled study investigating the safety, tolerability, and systemic absorption of 3% VivaGel^® when administered vaginally twice daily for 14 consecutive days in healthy, sexually active, HIV-negative young women. Of 61 women enrolled, seven were randomized to either 3% w/w VivaGel^® or VivaGel^® placebo in a 1:1 ratio, and 54 were randomized at a 1:1:1 ratio stratified by site to VivaGel^® placebo or HEC gel, with all three groups applying the product vaginally twice daily for 14 days.

The study completed follow-up on November 4, 2009. Results were first presented at the 2010 International Microbicides Conference held on May 22-25, 2010, in Pittsburgh, PA. The primary manuscript was published in AIDS on May 15, 2011. A total of six papers have been published from this study.

Primary Results
No serious adverse events or withdrawals due to adverse events were reported. Genitourinary symptoms were reported as follows: VivaGel (n = 17/22; 77.3%), VivaGel placebo (n = 14/21; 66.7%), and HEC (n = eight of 18; 44.4%; not significant, P = 0.1). The incidence of abnormal pelvic examination findings was similar across all gel arms of the study. Using pairwise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary adverse events compared with women in the HEC gel arm (0.297 versus 0.111 per 100 person-years, respectively; P = 0.003). Exposure to VivaGel and VivaGel placebo resulted in minor shifts in the vaginal microflora, but there was no overall impact on incidence of bacterial vaginosis as assessed by Nugent score. MTN-004 demonstrated that VivaGel was generally well-tolerated and comparable with the VivaGel placebo, although there was lower adherence and acceptability and a higher incidence of related genital adverse events compared to the HEC placebo gel.