Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial
Abstract 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 poten...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-14601-3 |
| _version_ | 1811241233200185344 |
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| author | Alex Castellarnau Graham P. Heery Aynaz Seta Carolyn A. Luscombe George R. Kinghorn Peter Button Philip McCloud Jeremy R. A. Paull |
| author_facet | Alex Castellarnau Graham P. Heery Aynaz Seta Carolyn A. Luscombe George R. Kinghorn Peter Button Philip McCloud Jeremy R. A. Paull |
| author_sort | Alex Castellarnau |
| collection | DOAJ |
| description | Abstract 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/ ). |
| first_indexed | 2024-04-12T13:33:24Z |
| format | Article |
| id | doaj.art-025250ececcc40b783bcdea2a8a0134f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T13:33:24Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-025250ececcc40b783bcdea2a8a0134f2022-12-22T03:31:06ZengNature PortfolioScientific Reports2045-23222022-06-0112111010.1038/s41598-022-14601-3Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trialAlex Castellarnau0Graham P. Heery1Aynaz Seta2Carolyn A. Luscombe3George R. Kinghorn4Peter Button5Philip McCloud6Jeremy R. A. Paull7Starpharma Pty LtdStarpharma Pty LtdStarpharma Pty LtdStarpharma Pty LtdUniversity of SheffieldMcCloud Consulting Group Pty LtdMcCloud Consulting Group Pty LtdStarpharma Pty LtdAbstract 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/ ).https://doi.org/10.1038/s41598-022-14601-3 |
| spellingShingle | Alex Castellarnau Graham P. Heery Aynaz Seta Carolyn A. Luscombe George R. Kinghorn Peter Button Philip McCloud Jeremy R. A. Paull Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial Scientific Reports |
| title | Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| title_full | Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| title_fullStr | Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| title_full_unstemmed | Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| title_short | Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| title_sort | astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial |
| url | https://doi.org/10.1038/s41598-022-14601-3 |
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