A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent bacterial vaginosis

Abstract

A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent bacterial vaginosis Jane R. Schwebkea, Belvia A. Carterb, Arthur S. Waldbaumc, Kathy J. Agnewd, Jeremy R.A. Paulle,*, Clare F. Pricee, Alex Castellarnaue, Philip McCloudf, George R. Kinghorng a Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA bWomen’s Physician Group, Memphis, TN, USA c Downtown Women’s Health Care, Denver, CO, USA d Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA e Starpharma Pty Ltd, Melbourne, VIC, Australia f McCloud Consulting Group, Sydney, NSW, Australia g Royal Hallamshire and Sheffield Teaching Hospitals, Sheffield, United Kingdom A R T I C L E I N F O Article history: Received 30 September 2020 Received in revised form 31 December 2020 Accepted 17 January 2021 Available online 19 January 2021 Keywords: Astodrimer Gel Bacterial vaginosis Biofilm Prevention Recurrent bacterial vaginosis SPL7013 VivaGel A B S T R A C T Objective: The objective of the study was to confirm the efficacy and safety of Astodrimer 1% Gel to prevent recurrence of bacterial vaginosis. Study design: 864 women with a diagnosis of bacterial vaginosis and a history of recurrent bacterial vaginosis were enrolled in North America and first received oral metronidazole (500 mg twice daily for 7 days). Women successfully treated with metronidazole were randomly assigned 1:1 to Astodrimer 1% Gel (N = 295) or placebo (N = 291) 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 included time to recurrence, and recurrence of subject-reported symptoms. Adverse events were monitored throughout the study. Results: Astodrimer 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) and Nugent score 7 10. Recurrence of subjectreported 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). Adverse events were infrequent, and rates were generally similar between placebo and astodrimer groups. Vulvovaginal candidiasis and urinary tract infection occurred more often in women receiving astodrimer.