A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

Waldbaum, Arthur; Schwebke, Jane R.; Paull, Jeremy Ra; Price, Clare; Edmondson, Stephanie R.; Castellarnau, Alex; McCloud, Philip; Kinghorn, G R

doi:10.1371/journal.pone.0232394

Cited by 24 publications

(51 citation statements)

References 26 publications

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Section: Discussionsupporting

confidence: 81%

“…Astodrimer sodium is a polyanionic dendrimer that blocks attachment of bacteria to cells, preventing formation of bacterial biofilms, which are central to the pathogenesis of BV and not targeted by existing therapies [ [12] , [13] , [14] , [15] , [16] ]. Astodrimer Gel achieved clinical cure in women with BV following a 7-day treatment course, with 50–74 % cured 2–5 days after end of treatment, and was well-tolerated and not systemically absorbed [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Schwebke

Carter

Waldbaum

et al. 2021

European Journal of Obstetrics & Gynecology and Reproductiv

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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

Schwebke

Carter

Waldbaum

et al. 2021

European Journal of Obstetrics & Gynecology and Reproductiv

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“…The potential advantages of astodrimer sodium over other technologies include its lack of systemic absorption following topical application (Chen et al, 2009;O'Loughlin et al, 2010;McGowan et al, 2011). In addition, the SI of astodrimer sodium for SARS-CoV-2 is high and in a vaginal gel formulation (10 mg/mL), the compound has been shown to be safe and effective in phase and large phase trials for treatment and prevention of BV (Schwebke et al, 2019;Chavoustie et al, 2020;Waldbaum et al, 2020) and is now marketed in Europe, Australia, New Zealand and several countries in Asia. Astodrimer sodium is also the active antiviral substance in VivaGel ® condom products that have marketing authorization in Europe, Japan, Australia/New Zealand and Canada.…”

Section: Discussionmentioning

confidence: 99%

Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro

Paull

Heery

Bobardt

et al. 2020

Preprint

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An effective response to the ongoing coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will require a range of complementary preventive modalities. The current studies were conducted to evaluate the in vitro SARS-CoV-2 antiviral activity of astodrimer sodium, a dendrimer with broad spectrum antimicrobial activity, including against enveloped viruses in in vitro and in vivo models, that is marketed for antiviral and antibacterial applications. We report that astodrimer sodium inhibits replication of SARS-CoV-2 in Vero E6 cells when added to cells 1-hour prior to or 1-hour post infection, with 50% effective concentrations reducing virus-induced cytopathic effect (EC50) ranging from 0.090 to 0.742 μM (0.002 to 0.012 mg/mL). The selectivity index (SI) in these assays was as high as 2197. Astodrimer sodium was also effective in a virucidal evaluation when mixed with virus for 1 hour prior to infection of cells (EC50 1.83 μM [0.030 mg/mL]). Results from a time of addition study, which showed infectious virus was below the lower limit of detection at all time points tested, were consistent with the compound inhibiting early virus entry steps. The data were similar for all investigations and were consistent with the potent antiviral activity of astodrimer sodium being due to inhibition of virus-host cell interactions, as previously demonstrated for other viruses. Further studies will confirm if astodrimer sodium binds to SARS-CoV-2 spike protein and physically blocks initial association of the virus with heparan sulfate proteoglycans on the host cell. Given the in vitro effectiveness and significantly high SI, astodrimer sodium warrants further investigation for potential as a nasally administered or inhaled antiviral agent for SARS-CoV-2 prevention and treatment applications.

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“…The results of reduced recurrence of BV at Week 16 are consistent with the ability of Astodrimer 1% Gel to achieve clinical cure of BV at the end of a 7-day treatment period, as demonstrated in phase 2 and 3 clinical studies. 17,18 The study was not stratified for race or other characteristics known to be associated with recurrence of BV, although treatment groups were well balanced with respect to baseline demographics. Subgroup analyses were exploratory in nature and results should be interpreted with caution.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

“…12,13,14,15,16 Astodrimer Gel was effective for treatment of women with BV, achieving clinical cure at the end of a 7-day treatment course, and was well-tolerated and not systemically absorbed. 17,18 Astodrimer Gel offers potential as a non-antibiotic approach suitable for longer-term administration to prevent recurrent BV. This adequately powered, placebo-controlled, phase 3 study assessed the efficacy and safety of Astodrimer 1% Gel for preventing recurrent BV.…”

Section: Introductionmentioning

confidence: 99%

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

Schwebke

Carter²,

Waldbaum

et al. 2020

Preprint

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Background: Bacterial 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. 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 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. 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), 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. Conclusions: Astodrimer 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.

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A phase 2, double-blind, multicenter, randomized, placebo-controlled, dose‑ranging study of the efficacy and safety of Astodrimer Gel for the treatment of bacterial vaginosis

Cited by 24 publications

References 26 publications

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

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

Virucidal and antiviral activity of astodrimer sodium against SARS-CoV-2 in vitro

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

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