Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial
Alex Castellarnau, Graham P Heery, Aynaz Seta, Carolyn A Luscombe, George R Kinghorn, Peter Button, Philip Mccloud, Jeremy R A Paull
Scientific Reports, doi:10.1038/s41598-022-14601-3
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 singlecentre, 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/). Epidemic and pandemic respiratory viral infections have caused significant public health problems worldwide. Recent examples of pandemic viruses include the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and influenza A virus (H1N1/pdm/09). Each of these pandemics has been associated with the emergence of..
Ethics approval and consent to participate. The investigation was approved by the Bellberry Human Research Ethics Committee (EC00469; SA, Australia) on 21 December 2020. All participants provided written informed consent prior to screening procedures.
Author contributions
Competing interests The authors JRAP, GPH and AS are paid employees of Starpharma Pty Ltd. The authors AC, CAL, GRK, PB and PMc are paid consultants to Starpharma Pty Ltd. JRAP, GPH, AS, AC and CAL are shareholders of Starpharma Holdings Ltd.
Additional information Correspondence and requests for materials should be addressed to J.R.A.P. Reprints and permissions information is available at www.nature.com/reprints. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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