An investigational vaginal gel significantly reduced urogenital chlamydia and gonorrhea in women at high risk for infection, compared with placebo, opening up new possibilities for an on-demand prevention option. Investigators of a randomized trial reported these findings in the American Journal of Obstetrics and Gynecology.
Rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are on the rise in the United States, despite wide availability of male and female condoms to prevent sexually transmitted infections. This suggests that women need a more discrete method that they can better control. Other vaginal microbicides developed over the last few decades haven’t performed well in protecting against STIs or HIV in clinical trials.
The slightly alkaline nature of human semen has the potential to neutralize vaginal pH after intercourse, creating a more vulnerable environment for STIs. EVO100 is an investigational antimicrobial, bioadhesive vaginal gel that contains L-lactic acid, citric acid, and potassium bitartrate. In preclinical studies, it was highly effective at buffering the alkaline properties of human semen and maintaining vaginal pH levels. Patients generally tolerated it well, aside from some reports of vaginal itching and burning.
In the AMPREVENCE study, a double-blinded, placebo-controlled, randomized, phase 2b/3 trial, Todd Chappell, MD, of Adams Patterson Gynecology & Obstetrics, Memphis, and colleagues tested the efficacy and safety of EVO100 to prevent chlamydia and gonorrhea.
Investigators randomized 1:1,860 healthy, sexually active women to receive either EVO100 (n = 426) or placebo (n = 434). Participants had either been diagnosed or treated for these STIs up to 16 weeks prior to enrollment. Among those enrolled, 335 women in the EVO100 arm and 335 women in the placebo arm completed the study.
From this cohort, 764 women (EVO100: n = 376; placebo: n = 388) reported any use of either product. These women represented the “safety analysis population,” a predefined population for statistical analysis.
Participants averaged nearly 28 years of age, had a median body mass index of 28.9 kg/m2, and represented several racial/ethnic groups: White (54.3% [467/860]), African American (41.6% [358/860]), and non-Hispanic/Latinx ethnicity (67.1% [577/860]).
The women were instructed to apply the drug within 1 hour of initiating sexual intercourse. Investigators scheduled follow-up visits every 4 weeks during the 16-week study period, to obtain repeat CT/GC assessments, review diary entries, and to collect information about adverse effects and use of concomitant medications. During enrollment, participants consented to return to the clinic at each study visit. If a woman missed a visit, the study site would follow-up by telephone after the missed assessment visit.
Participants reported a mean number of 16 coital events (EVO100, 15.7 [13.5]; placebo, 16.3 [15.8]). EVO100 significantly reduced STI incidence for both types of STIs. CT infection rates among EVO100 users was 4.8% (14/289), half of what it was in placebo users (9.7% [28/290]) (P = .0256). The investigational method was even more successful in GC-analysis–eligible women: infection rates averaged 0.7% (2/280), compared with 3.2% (9/277) in the placebo group, a relative risk reduction of 78% (P = .0316).
Examining electronic diary entries of the participants, investigators reported similar adherence rates among the two treatment arms. However, additional sensitivity analyses in CT-eligible and GC-eligible populations on adherence yielded notably different results.
EVO100 users in the CT population who used the product as directed 100% of the time were significantly less likely to become infected, compared with the placebo group (2.3% vs. 16.9%, P = .0012). However, investigators found no significant differences in infection rates among women with poorer adherence rates in the two groups. Comparatively, they found no major differences in GC infection rates between the control and EVO100 groups, regardless of adherence rates, likely because of the small number of GC infections reported. Observed adverse events correlated with the drug’s known safety profile.
Most of the participants said they would likely recommend EVO100 to other women and continue using this preventive treatment.
A small GC subgroup caused by fewer infection cases and reliance on participant self-reporting of coital incidents may have limited the study’s results. “While use of the electronic diaries is helpful for collection of study data, it may encourage compliance and efficacy that may be higher in the ‘real-world’ population outside of the setting of a clinical trial,” noted Dr. Chappell and colleagues.
According to the investigators, this is the first prospective, randomized trial to study the use of an antimicrobial bioadhesive vaginal gel for preventing CT and GC infection. “EVO100 has the potential of fulfilling an unmet need in women’s sexual health as a new on-demand, woman-controlled option that reduces the risk of urogenital CT and GC infections,” the authors concluded.
The Food and Drug Administration has already approved EVO100 as a contraceptive option (Phexxi), Dr. Chappell said in an interview. Next steps are to conduct a phase 3 trial, which is currently underway. “If the findings are positive, we will submit to the FDA for review and approval of EVO100” for preventing these STIs.
These are promising results, Catherine Cansino, MD, MPH, an associate clinical professor with the department of obstetrics and gynecology at the University of California, Davis, said in an interview. It’s always helpful to look at effective treatments, “especially those that aren’t traditional antibiotics in order to decrease the risk of antibiotic resistance,” said Dr. Cansino, who was not part of the study. This is why EVO100 is such an attractive option.
Future studies should look at a broader population, she continued. “The population this study looked at is not the general population – these women had an infection at some point, previously,” which means they are potentially at higher risk for reinfection. “Looking at what their likelihood is of getting infected again, it’s hard to know if this would be the same or different from the general population.” If the drug appears to cause a decrease in new infections, the relative risk reduction is actually greater than what’s reported. If the reinfection rate for this population is lower because people who’ve had infections are practicing safer sex, the relative risk reduction would be lower, explained Dr. Cansino.
Dr. Chappell and several coauthors received research funding from Evofem Biosciences.