A Phase 3, Randomized, Controlled Trial of Astodrimer 1% Gel for Preventing Recurrent Bacterial Vaginosis

AbstractBackgroundBacterial vaginosis is highly recurrent after antibiotic treatment, and prevention represents an unmet medical need. Astodrimer 1% Gel contains a novel dendrimer that blocks bacterial attachment and has been shown to effectively treat bacterial vaginosis.ObjectiveThe objective of the study was to confirm the efficacy and safety of Astodrimer 1% Gel to prevent recurrence of bacterial vaginosis.Study Design864 women with a current episode of bacterial vaginosis and a history of recurrent bacterial vaginosis were enrolled in the open-label phase of the study to receive oral metronidazole (500 mg twice daily for 7 days) at 77 centers in North America. 586 women successfully treated with metronidazole were randomly assigned 1:1 to Astodrimer 1% Gel or placebo at a dose of 5 g vaginally every second day for 16 weeks, and followed for a further 12 weeks off-treatment. The primary endpoint was recurrence of bacterial vaginosis (presence of ≥3 Amsel criteria) at or by Week 16. Secondary endpoints of recurrence of bacterial vaginosis at or by Week 16 included time to recurrence, subject-reported symptoms of bacterial vaginosis, individual Amsel criteria, Nugent score 7-10, and the composite of Amsel criteria and Nugent score. Adverse events were monitored throughout the study.ResultsAstodrimer 1% Gel was superior to placebo for the primary and many secondary efficacy measures. At or by Week 16, bacterial vaginosis recurred in 44.2% (130/294) of women receiving astodrimer and 54.3% (158/291) receiving placebo (P = .015). Time to recurrence of bacterial vaginosis was significantly longer for women receiving astodrimer compared with placebo (Kaplan-Meier survival curves, P = .007). Recurrence of subject-reported symptoms at or by Week 16 was also significantly lower in the astodrimer arm compared with placebo (vaginal odor and/or discharge, 27.9% [75/269] vs 40.6% [108/266], P = .002). A significantly lower proportion of patients receiving astodrimer compared with placebo had recurrence of bacterial vaginosis at or by Week 16 by other secondary measures, including individual Amsel criteria (vaginal discharge and clue cells), Nugent score 7-10, and composite of Nugent score and Amsel criteria. Recurrence of subject-reported bacterial vaginosis symptoms, vaginal odor and/or discharge, was significantly lower in the astodrimer arm compared with placebo up to 8 weeks after cessation of therapy (36.1% [97/269] vs 45.5% [121/266], P = .027). During the 12-week follow-up, recurrence of ≥3 Amsel criteria after cessation of therapy in women given astodrimer was lower than in those given placebo, but the differences were not statistically significant.Adverse events were infrequent, and rates were similar between placebo and astodrimer groups, except for vulvovaginal candidiasis and urinary tract infection, which occurred more often in women receiving astodrimer.ConclusionsAstodrimer 1% Gel, administered every second day for 16 weeks, was effective and superior to placebo for prevention of recurrent bacterial vaginosis in women with a history of recurrent BV, and was well-tolerated. These results support a role for Astodrimer 1% Gel as an effective long-term treatment to prevent recurrent bacterial vaginosis that avoids potential issues associated with conventional antibiotics.