Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial.

Astodrimer sodium is a dendrimer molecule with antiviral and virucidal activity against SARS-CoV-2 and other respiratory viruses in vitro, and has previously been shown to be safe and well tolerated, and not systemically absorbed, when applied to the vaginal mucosa. To investigate its potential utility as a topical antiviral, astodrimer sodium has been reformulated for application to the nasal mucosa to help reduce viral load before or after exposure to respiratory infection. The current investigation assessed the safety, tolerability and absorption of astodrimer sodium 1% antiviral nasal spray. This was a single-centre, double-blinded, randomized, placebo-controlled, exploratory clinical investigation. Forty healthy volunteers aged 18 to 65 years with no clinically significant nasal cavity examination findings were randomized 3:1 to astodrimer sodium nasal spray (N = 30) or placebo (N = 10) at an Australian clinical trials facility. An initial cohort of participants (N = 12 astodrimer, N = 4 placebo) received a single application (one spray per nostril) to assess any acute effects, followed by a washout period, before self-administering the spray four times daily for 14 days to represent an intensive application schedule. Extent of absorption of astodrimer sodium via the nasal mucosa was also assessed in this cohort. A second cohort of participants (N = 18 astodrimer, N = 6 placebo) self-administered the spray four times daily for 14 days. The primary endpoint was safety, measured by frequency and severity of treatment emergent adverse events (TEAEs), including clinically significant nasal cavity examination findings, in the safety population (all participants randomized who administered any spray). Participants were randomized between 6 January 2021 and 29 March 2021. TEAEs occurred in 8/10 (80%) participants in the placebo arm and 19/30 (63.3%) participants in the astodrimer sodium arm; all were of mild intensity. TEAEs considered potentially related to study product occurred in 5/10 (50%) participants receiving placebo and 10/30 (33.3%) of participants receiving astodrimer sodium. No participants experienced serious AEs, or TEAEs leading to withdrawal from the study. No systemic absorption of astodrimer sodium via the nasal mucosa was detected. Astodrimer sodium nasal spray was well tolerated and is a promising innovation warranting further investigation for nasal administration to potentially reduce infection and spread of community acquired respiratory virus infections.Trial Registration: ACTRN12620001371987, first registered 22-12-2020 (Australia New Zealand Clinical Trials Registry, https://anzctr.org.au/ ).

A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent 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 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 subject-reported 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. 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.

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

BACKGROUND: Astodrimer Gel contains a novel dendrimer intended to treat and prevent bacterial vaginosis. We assessed the efficacy and safety of Astodrimer Gel for treatment of bacterial vaginosis. METHODS: 132 women with bacterial vaginosis were randomized 1:1:1:1 to Astodrimer 0.5% (N = 34), 1% (N = 33), or 3% (N = 32) Gel or hydroxyethyl cellulose placebo gel (N = 33) at a dose of 5 g vaginally once daily for 7 days at 6 centers in the United States. The primary endpoint was clinical cure (no bacterial vaginosis vaginal discharge and no more than one of 1) vaginal pH ≥4.5; 2) ≥20% clue cells; or 3) positive whiff test) at study days 21-30. Secondary analyses included clinical cure at study days 9-12, patient-reported symptoms, acceptability and adverse events. RESULTS: The Astodrimer 1% Gel dose was superior to placebo for the primary and selected secondary efficacy measures in the modified intent-to-treat population. Clinical cure rates at day 9-12 were superior to placebo for the Astodrimer 3%, 1% and 0.5% Gel groups (62.5% [15/24; P = .002], 74.1% [20/27; P < .001], and 55.2% [16/29; P = .001], respectively, vs. 22.2% [6/27]). At day 21-30, clinical cure rates were 46.2% (12/26) for the 1% dose vs. 11.5% for placebo (3/26; P = .006). A greater proportion of patients reported absence of vaginal discharge and vaginal odor at day 9-12 and day 21-30 for Astodrimer Gel groups compared with placebo. Adverse events considered potentially treatment-related occurred in only 25% of Astodrimer Gel-treated patients vs. 22% of placebo patients. CONCLUSION: Astodrimer Gel once daily for 7 days was superior to placebo for treatment of bacterial vaginosis and was well-tolerated. The 1% dose consistently showed the strongest efficacy across endpoints. These results support a role for Astodrimer Gel, 1%, as an effective treatment for bacterial vaginosis.

Two phase 3, double-blind, placebo-controlled studies of the efficacy and safety of Astodrimer 1% Gel for the treatment of bacterial vaginosis.

OBJECTIVE: Astodrimer is a dendrimer formulated in a vaginal gel to treat bacterial vaginosis (BV) and prevent recurrence. The objective of these studies was to confirm the efficacy and safety of Astodrimer 1 % Gel for treatment of BV. STUDY DESIGN: Women with bacterial vaginosis were randomized 1:1 to Astodrimer 1 % Gel (Study 1 conducted in the United States, N = 127; Study 2 conducted in the United States, Germany and Belgium, N = 128) or placebo gel (Study 1, N = 123; Study 2, N = 123) at a dose of 5 g vaginally once daily for 7 days. The primary endpoint was clinical cure, defined as i) absence of bacterial vaginosis vaginal discharge; ii) <20 % clue cells; and iii) negative whiff test at day 9-12. Secondary efficacy analyses included clinical cure at day 21-30. Other endpoints at days 9-12 and 21-30 included Nugent cure (Nugent score ≤3), absence of symptoms, and adverse events. The primary analysis in the modified intent-to-treat population used the Cochran Mantel Haenszel test stratified by analysis center with a two-sided significance level of α = .05. RESULTS: Astodrimer 1 % Gel was superior to placebo for the primary and selected secondary efficacy measures. Clinical cure rates at day 9-12 were 50.4 % (59/117) vs 16.5 % (19/115, P < .001) (Study 1) and 56.7 % (68/120) vs 21.4 % (25/117, P < .001) (Study 2) for astodrimer vs placebo. At day 21-30, clinical cure results showed a similar trend but the difference to placebo was not statistically significant. Nugent cure rates at day 9-12 were 12.8 % (15/117) vs 2.6 % (3/115, P = .004) (Study 1) and 13.3 % (16/120) vs 5.1 % (6/117, P = .030) (Study 2) for astodrimer vs placebo. A greater proportion of women receiving astodrimer reported absence of vaginal discharge and absence of vaginal odor at day 9-12 and day 21-30 compared with placebo. Adverse events were generally mild and self-limiting. For the combined studies, adverse events potentially related to treatment occurred in 14.7 % (37/252) of astodrimer patients vs 9.4 % (23/244) for placebo, including vulvovaginal candidiasis reported for 2.4 % (6/252) of astodrimer patients. CONCLUSION: These results support a role for Astodrimer 1 % Gel as an effective, safe and well-tolerated treatment for women with bacterial vaginosis.

Three phase III randomized controlled trials of topical resiquimod 0.01-percent gel to reduce anogenital herpes recurrences.

Resiquimod, a Toll-like receptor 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 acquired immune response. Animal and phase II human trials showed posttreatment efficacy in reducing recurrent herpes lesion days and/or time to first recurrence. Three phase III randomized, double-blind, vehicle-controlled trials of topical resiquimod to reduce anogenital herpes recurrences were conducted in healthy adults with ≥4 recurrences within the prior year. Participants applied resiquimod 0.01% gel or vehicle gel 2 times per week for 3 weeks to each recurrence for 12 months. Trials 1 and 2 had 2:1 resiquimod-vehicle randomization. Trial 3 had 1:1:1 randomization for resiquimod and 500 mg valacyclovir orally twice daily for 5 days (RESI-VAL), resiquimod and oral placebo (RESI-PLA), and vehicle and oral placebo (VEH-PLA). The median time to first recurrence was similar for resiquimod and vehicle (trial 1, 60 and 56 days, P=0.7; trial 2, 54 and 48 days, P=0.47; trial 3, 51 [RESI-VAL], 55 [RESI-PLA], and 44 [VEH-PLA] days, P=not significant [NS]). The median time to healing of initial treated recurrence was longer for resiquimod (trial 1, 18 compared to 10 days, P<0.001; trial 2, 19 compared to 13 days, P=0.16; trial 3, 14 [RESI-VAL], 16 [RESI-PLA], and 8 [VEH-PLA] days, P<0.001). In trials 1 and 2, moderate to severe erythema and erosion/ulceration at the application site were more common in resiquimod recipients. In conclusion, no posttreatment efficacy of resiquimod 0.01% gel was observed. Increased application site reactions and initial recurrence healing time are consistent with resiquimod-induced cytokine effects.

Concordance between Neisseria gonorrhoeae genotypes recovered from known sexual contacts.

Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) is a highly discriminatory molecular typing procedure that provides precise and unambiguous strain characterization. Since molecular typing can complement contact tracing for reconstructing gonorrhea sexual networks, the concordance between the NG-MAST genotypes of pairs of N. gonorrhoeae isolates from recent sexual contacts was examined. Among 72 pairs of gonococci from recent sexual contacts, the genotypes of each pair were concordant in 65 cases (90.3%). In two further pairs, the isolates from sexual contacts differed by only a single nonsynonymous substitution in the porin gene, and in both of these pairs, the isolates were the same by opa typing. The other five nonconcordant pairs of isolates were clearly different strains. opa typing data were available for 51 of the pairs of isolates from sexual contacts, and concordant opa types were obtained in 38 cases (74.5%). NG-MAST should therefore be better than opa typing at identifying recent sexual contacts and has the important advantage over opa typing of being a more precise method of strain characterization.

BD ProbeTec ET assay for the diagnosis of gonorrhoea in a high-risk population: a protocol for replacing traditional microscopy and culture techniques.

OBJECTIVES: To evaluate the Neisseria gonorrhoeae Becton Dickinson (BD) ProbeTec strand displacement assay (SDA) on female endocervical swab and male first void urine against culture for Neisseria gonorrhoeae on female endocervical and urethral swab for the diagnosis of N gonorrhoeae infection in genitourinary medicine (GUM) attendees. To determine an algorithm for implementation of N gonorrhoeae infection screening by SDA in these patients taking account of the desirability of having a N gonorrhoeae isolate in people with N gonorrhoeae infection. METHODS: Initially, 1582 patients attending the GUM clinic were tested for N gonorrhoeae infection by SDA and routine microscopy, and culture. On the basis of the results, a protocol for diagnosis of N gonorrhoeae infection by SDA, with culture specimens only from patients with a listed risk factor for acquiring N gonorrhoeae infection, was devised and implemented. A post implementation audit was done to assess the effectiveness of this protocol for routine service use. RESULTS: There was good concurrence between the N gonorrhoeae SDA and culture results with a N gonorrhoeae infection prevalence rate of 3.4% by both methods. All men and 85% of women with N gonorrhoeae infection had an identifiable risk factor for acquiring infection. Overall, 38% men and 60% women attending the GUM clinic had this listed risk factor for acquiring N gonorrhoeae. Post implementation audit confirmed the initial findings. CONCLUSION: Nucleic acid amplification techniques like the SDA are sensitive and specific for diagnosis of N gonorrhoeae. We were able to list certain risk factors, which were predictive of those patients most likely to have N gonorrhoeae infection. To obtain timely sensitivity data, a culture specimen should also be submitted at the same time from patients deemed to have a listed risk factor for acquiring Neisseria gonorrhoeae infection.

Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database.

OBJECTIVE: To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics. DESIGN: Population based study. SETTING: UK primary care. PARTICIPANTS: Patients registered in the UK general practice research database. MAIN OUTCOME MEASURES: Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care. RESULTS: An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s. CONCLUSIONS: A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections.

Debate: the argument for. Should all pregnant women be offered type-specific serological screening for HSV infection?

The challenge for the prevention of acquisition of neonatal herpes is to identify those mothers at risk of acquiring herpes simplex virus (HSV) infection in pregnancy, and then to apply interventions to reduce this risk. Existing strategies to prevent neonatal herpes are based on recognition of clinical lesions in mothers at term, but these approaches may be of limited effectiveness, given that most cases of neonatal herpes result from unrecognized maternal acquisition of HSV in late pregnancy. The availability of type-specific serological tests for HSV-2 and HSV-1 now allows identification of at-risk pregnancies, and can enhance strategies to prevent both maternal and neonatal herpes infection. This may help to reduce the need for a Caesarean section, while promoting individual and public health gains.