EVO100 prevents chlamydia and gonorrhea in women at high risk of infection

Background

According to the Centers for Disease Control and Prevention, rates of infection for Chlamydia trachomatis and Neisseria gonorrhoeae are increasing in the United States. EVO100 is an investigational antimicrobial, pH-modulating, vaginal gel with active ingredients L-lactic acid, citric acid, and potassium bitartrate that is being evaluated for the prevention of sexually transmitted infections.

Objective

The objective of this phase 2B/3 study was to assess the efficacy and safety of EVO100 for the prevention of chlamydia and gonorrhea.

Study Design

AMPREVENCE was a double-blinded, placebo-controlled, multicenter study based in the United States conducted over approximately 16 weeks in women at the age of 18 to 45 years who were at risk of urogenital chlamydia and gonorrhea infection. Enrolled women had been diagnosed as having and treated for chlamydia or gonorrhea ≤16 weeks before enrollment. Women received either EVO100 or placebo vaginal gel and were instructed to apply the study drug immediately before or up to 1 hour before each act of vaginal sexual intercourse. The primary and secondary endpoints were the prevention of urogenital chlamydia and gonorrhea, respectively. Exploratory outcomes include women’s overall satisfaction with EVO100.

Results

In total, 860 women were randomized 1:1 to receive EVO100 (n=426) or placebo (n=434), and 764 women (EVO100, n=376; placebo, n=388) were documented as using the study drug at least once. Baseline characteristics were similar between treatment arms. Overall, women had a mean age of 27.7 years (standard deviation, 6.9) and body mass index of 28.9 kg/m² (standard deviation, 8.0). Most women were of White (54.3% [467 of 860]) or African American (41.6% [358 of 860]) race and of non-Hispanic/Latina ethnicity (67.1% [577 of 860]). The chlamydia infection rate in EVO100 users was 4.8% (14 of 289) compared with 9.7% (28 of 290) among placebo users (P=.0256), representing a relative risk reduction of 50%. For gonorrhea, the infection rate was 0.7% (2 of 280) in the EVO100 arm compared with 3.2% (9 of 277) in the placebo arm (P=.0316), representing a relative risk reduction of 78%. Increased efficacy was observed with increased adherence, and chlamydia infection rates were significantly reduced with increased adherence in the EVO100 group compared with placebo. Across both arms, there were similar rates of all-cause adverse events (EVO100, 21.3% [80 of 376]; placebo, 20.4% [79 of 388]) and treatment-related adverse events (EVO100, 7.2% [27 of 376]; placebo, 7.5% [29 of 388]). The most common adverse events in the EVO100 arm were vulvovaginal candidiasis (5.1% [19 of 376]), vaginal discharge (3.2% [12 of 376]), and urinary tract infection (3.2% [12 of 376]) and, in the placebo arm, bacterial vaginosis (4.6% [18 of 388]), urinary tract infection (2.6% [10 of 388]), and vaginal discharge (2.6% [10 of 388]). Few women discontinued owing to adverse events in either arm (EVO100, 1.1% [4 of 376]; placebo, 1.5% [6 of 388]). No treatment-related serious adverse events were reported. Most EVO100 users (88%) were satisfied or very satisfied with EVO100 after 16 weeks of use.

Conclusion

EVO100 significantly reduced the risk of chlamydia and gonorrhea infections in women at high risk of Chlamydia trachomatis and Neisseria gonorrhoeae infection and was well tolerated, with observed adverse events consistent with its known safety profile.

Introduction

In 2018, the United States Centers for Disease Control and Prevention reported that Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) were the first and second most common notifiable conditions in the United States, respectively.¹ Despite the availability of the male and female condoms for prevention of sexually transmitted infections (STIs), the increasing incidence of CT and GC infection suggests that there is an urgent need for new prevention strategies, especially a method that is discrete and woman controlled. Because CT and GC infections in women are often asymptomatic and may go undetected, substantial consequences may result if left untreated.¹ Furthermore, there is a higher risk of CT or GC infection in women who were treated for CT or GC infection during the preceding several months. The subsequent infection may result from a repeat infection through an untreated partner or exposure through a new partner.

AJOG at a Glance

The increasing rates of chlamydia and gonorrhea infection are urgent public health concerns; in this study, we sought to determine whether EVO100, an investigational antimicrobial, pH-modulating vaginal gel, reduces the risk of urogenital Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in women at high risk of CT or GC infection.

Results from our study show that EVO100 was well tolerated and was effective in reducing the risk of CT and GC infection, with significantly lower rates of CT (P=.0256) and GC (P=.0316) infection in women receiving EVO100 than placebo users.

There is a need for a discrete, woman-controlled method for CT and GC prevention. Several other vaginal microbicides have been developed, but have failed to protect women after further investigation. Results from our study show that EVO100 significantly reduces the risk of CT and GC infection in women at high risk of CT or GC infection.

An acidic vaginal pH and colonization of lactobacilli species in the vaginal mucosa are components of the multifaceted antimicrobial defense mechanisms in the vaginal fluid, which include the production of protective bacteriostatic and bactericidal compounds by lactobacillus species.2, 3, 4, 5, 6 It is thought that the naturally acidic vaginal environment may inhibit the acquisition of common STIs, including CT and GC.10, 11, 7, 8, 9 A prospective case-controlled study found that independent of other factors, women with CT infections were 6 times more likely to have pH>4.5 than controls.⁷ In another study, 76% of women exposed to GC through an infected partner with vaginal pH 5.0 to 6.5 subsequently developed GC infection compared with 48% of women whose vaginal pH was <5.0.¹¹ In the past 2 decades, there have been several vaginal microbicidal formulations developed, and although there were promising initial preclinical studies for several agents, many have failed to protect women against STIs or HIV acquisition or lacked funding for further investigation.^12,13

EVO100 is an investigational antimicrobial vaginal pH modulator being evaluated for the prevention of STIs. It is a novel, woman-controlled, water-based vaginal gel containing 3 active ingredients, L-lactic acid, citric acid, and potassium bitartrate. Previous studies have shown that EVO100 is well tolerated with vaginal itching and burning as the most commonly reported safety events.^14,15 Colposcopic evaluation indicated no vulvar, vaginal, or cervical signs of irritation in women who used EVO100 for 6 consecutive days.¹⁶ It has unique pH-modulating, acid-buffering properties to maintain the acidic vaginal environment, even in the presence of alkaline semen.^17,18 Human semen is slightly alkali (pH, 7.2–8.0) and can neutralize the vaginal pH following intercourse.¹⁹ Preclinical testing showed that EVO100 has highly effective acid-buffering properties and can buffer twice the volume of semen to maintain pH <4.5.¹⁷ In a phase 1 dose-finding study, a single 5 g dose of EVO100 significantly reduced mean vaginal pH from baseline by −0.44 within an hour of administration and maintained reduced pH from baseline for 7 days after use. In comparison, vaginal pH in placebo users fluctuated above and below baseline pH levels throughout the 7-day study period.¹⁴ During development, it was found that EVO100 exhibited microbicidal activity against CT and GC, without impacting the beneficial native lactobacilli, and results from a phase 1 study showed that EVO100 use reduced the concentration of Gardnerella vaginalis.^15,20,21 Disruption of the naturally occurring human vaginal microflora and acidic vaginal environment has been shown to be linked to an increased risk of STIs, including CT and GC.22, 23, 24, 25, 26, 27 The objective of this study was to evaluate the efficacy of EVO100 in reducing urogenital CT and GC infection in sexually active women at high risk of CT or GC infection.