Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial

{ 'indexed': {'date-parts': [[2024, 9, 7]], 'date-time': '2024-09-07T00:30:30Z', 'timestamp': 1725669030258}, 'reference-count': 30, 'publisher': 'MDPI AG', 'issue': '9', 'license': [ { 'start': { 'date-parts': [[2024, 9, 6]], 'date-time': '2024-09-06T00:00:00Z', 'timestamp': 1725580800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'name': 'Starpharma Pty Ltd.'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Background/Objectives: Dendrimer-based astodrimer sodium nasal spray was assessed for ' 'its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe ' 'illness for vulnerable groups. Methods: This was a randomised, double-blind, ' 'placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray ' 'in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. ' 'Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or ' 'placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load ' 'determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area ' 'under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUCd1–8). The primary analysis ' 'population was the modified intent-to-treat population (mITT: all randomised participants ' 'exposed to the study treatment who had at least one post-baseline viral load determination). ' 'Safety analyses included all randomised participants exposed to the study treatment. Study ' 'registration: ISRCTN70449927; Results: 231 participants were recruited between 9 January and ' '20 September 2023. The safety population comprised 109 and 113 participants randomised to ' 'astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer ' 'sodium nasal spray reduced the SARS-CoV-2 burden (vAUCd1–8) vs. placebo in non-hospitalised ' 'COVID-19 patients aged 16 years and over (−1.2 log10 copies/mL × Day). The reduction in ' 'SARS-CoV-2 load was statistically significant in those aged 45 years and older (−3.7, p = ' '0.017) and the effect increased in older age groups, including in those aged 65 years and ' 'older (−7.3, p = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance ' 'and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 ' 'participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to ' 'treatment. Most AEs were of mild severity and occurred at similar rates in both treatment ' 'arms. Conclusions: Astodrimer nasal spray reduces viral burden and accelerates viral ' 'clearance, especially in older populations, and is well tolerated.</jats:p>', 'DOI': '10.3390/pharmaceutics16091173', 'type': 'journal-article', 'created': {'date-parts': [[2024, 9, 6]], 'date-time': '2024-09-06T09:02:28Z', 'timestamp': 1725613348000}, 'page': '1173', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A ' 'Randomised, Double-Blinded, Placebo-Controlled Trial', 'prefix': '10.3390', 'volume': '16', 'author': [ { 'given': 'Stephen', 'family': 'Winchester', 'sequence': 'first', 'affiliation': [ { 'name': 'Frimley Health National Health Service Foundation Trust, ' 'Camberley GU16 7UJ, UK'}]}, { 'given': 'Alex', 'family': 'Castellarnau', 'sequence': 'additional', 'affiliation': [{'name': 'Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia'}]}, { 'given': 'Kashif', 'family': 'Jabbar', 'sequence': 'additional', 'affiliation': [ { 'name': 'Ashford and St. Peter’s Hospitals National Health Service ' 'Foundation Trust, Chertsey KT16 0PZ, UK'}]}, { 'given': 'Meera', 'family': 'Nadir', 'sequence': 'additional', 'affiliation': [ { 'name': 'Ashford and St. Peter’s Hospitals National Health Service ' 'Foundation Trust, Chertsey KT16 0PZ, UK'}]}, { 'given': 'Kapila', 'family': 'Ranasinghe', 'sequence': 'additional', 'affiliation': [ { 'name': 'Ashford and St. Peter’s Hospitals National Health Service ' 'Foundation Trust, Chertsey KT16 0PZ, UK'}]}, { 'given': 'Xavier', 'family': 'Masramon', 'sequence': 'additional', 'affiliation': [ { 'name': 'Servicio de Asesoría a la Investigación y Logística (SAIL), ' '08027 Barcelona, Spain'}]}, { 'given': 'George R.', 'family': 'Kinghorn', 'sequence': 'additional', 'affiliation': [ { 'name': 'Royal Hallamshire Hospital, University of Sheffield, Western ' 'Bank, Sheffield S10 2TN, UK'}]}, { 'ORCID': 'http://orcid.org/0000-0003-2856-6180', 'authenticated-orcid': False, 'given': 'Isaac', 'family': 'John', 'sequence': 'additional', 'affiliation': [ { 'name': 'Ashford and St. Peter’s Hospitals National Health Service ' 'Foundation Trust, Chertsey KT16 0PZ, UK'}, {'name': 'Royal Holloway, University of London, Egham TW20 0EX, UK'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9981-421X', 'authenticated-orcid': False, 'given': 'Jeremy R. A.', 'family': 'Paull', 'sequence': 'additional', 'affiliation': [{'name': 'Starpharma Pty Ltd., Abbotsford, VIC 3067, Australia'}]}], 'member': '1968', 'published-online': {'date-parts': [[2024, 9, 6]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': 'm1728', 'DOI': '10.1136/bmj.m1728', 'article-title': 'Reducing Risks from Coronavirus Transmission in the Home-the Role of ' 'Viral Load', 'volume': '369', 'author': 'Little', 'year': '2020', 'journal-title': 'BMJ'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '16587', 'DOI': '10.1073/pnas.2009799117', 'article-title': 'Syrian Hamsters as a Small Animal Model for SARS-CoV-2 Infection and ' 'Countermeasure Development', 'volume': '117', 'author': 'Imai', 'year': '2020', 'journal-title': 'Proc. Natl. Acad. Sci. 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