Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial
Stephen Winchester, Alex Castellarnau, Kashif Jabbar, Meera Nadir, Kapila Ranasinghe, Xavier Masramon, George R Kinghorn, Isaac John, Jeremy R A Paull
Pharmaceutics, doi:10.3390/pharmaceutics16091173
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 (vAUC d1-8 ). The primary analysis population was the modified intent-totreat 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 (vAUC d1-8 ) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (-1.2 log 10 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.
Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author. Acknowledgments: First and foremost, we sincerely thank all of the study participants for their participation. We also thank Ana Glennon for her contribution to implementing the study, following up with participants and collecting and cleaning data. Thanks to Samiya Hussain for monitoring and supporting the clinical site and contributing to data cleaning activities. We are grateful to Amelia Spiers for her support with data entry and cleaning. We also thank Freda Gomes for her assistance in communicating with the ethics committee. Our gratitude extends to Mario Garcia for his support with data cleaning, statistical programming and analysis. We acknowledge Mireia Riera for coding adverse events, medical history conditions and concomitant medications. We thank Adrian Wildfire and Martin Schutten of CHIMunomics Ltd. for their help interpreting the study results. Additionally, we thank Graham Heery, Aynaz Seta and Arnulf Company for their support in making the study product available, and Renée Brown and Sivananthan Baalakumaran for their quality assurance oversight. We are also grateful to all site and laboratory staff who contributed to this study. Finally, we sincerely thank the..
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'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 '
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'arms. Conclusions: Astodrimer nasal spray reduces viral burden and accelerates viral '
'clearance, especially in older populations, and is well tolerated.</jats:p>',
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'Anosmia Followed by Severe Neurological Disorders?',
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'author': 'Anwar',
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'Goldberg, T.E., Devanand, D.P., and Overdevest, J.B. (2023). Olfaction '
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'DOI': '10.3389/fnins.2023.1198267'}],
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