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. 2024 Sep 6;16(9):1173.
doi: 10.3390/pharmaceutics16091173.

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

Stephen Winchester  1 , Alex Castellarnau  2 , Kashif Jabbar  3 , Meera Nadir  3 , Kapila Ranasinghe  3 , Xavier Masramon  4 , George R Kinghorn  5 , Isaac John  3   6 , Jeremy R A Paull  2
Affiliations

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

Stephen Winchester et al. Pharmaceutics. .

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; SPL7013; antiviral; astodrimer; dendrimer; intranasal spray.

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Conflict of interest statement

J.R.A.P. is a paid employee and equity holder of Starpharma Pty Ltd. A.C., G.R.K. and S.W. are paid consultants to Starpharma Pty Ltd. I.J. is the founder and CEO of Metanoic Health Ltd., which received payment from Starpharma Pty Ltd. for the implementation and management of the investigation. S.W. is a paid consultant to Metanoic Health Ltd. X.M. is co-founder and paid employee of Servicio de Asesoría a la Investigación y Logística (SAIL), which received payment from Starpharma Pty Ltd. for providing statistical services for the investigation. K.J., M.N. and K.R. have no competing interests to declare.

Figures

Figure 1
Figure 1
Representation of astodrimer sodium dendrimer structure and mechanism of antiviral action.
Figure 2
Figure 2
Schematic of study design.
Figure 3
Figure 3
CONSORT flow diagram.
Figure 4
Figure 4
SARS-CoV-2 RNA load from Day 1 through Day 8 (vAUCd1–8) by treatment and age group. Compared using least squares means difference. * p < 0.05.
Figure 5
Figure 5
Proportion of participants with negative RT-qPCR test at or by Day 8, by treatment and age group. Compared using Fisher’s exact text. * p < 0.05.
Figure 6
Figure 6
Time in days from baseline to negative RT-qPCR (55 Y+). Compared using log-rank test. * p < 0.05.
Figure 7
Figure 7
SARS-CoV-2 RNA load at each determination by treatment and age group: (a) all ages (mITT), (b) 45 Y+ and (c) 65 Y+. Compared using least squares means difference. * p < 0.05.
Figure 7
Figure 7
SARS-CoV-2 RNA load at each determination by treatment and age group: (a) all ages (mITT), (b) 45 Y+ and (c) 65 Y+. Compared using least squares means difference. * p < 0.05.
Figure 8
Figure 8
Proportion of participants with (a) loss of sense of smell (anosmia), (b) loss of sense of taste (ageusia) and (c) loss of sense of smell (anosmia) and/or taste (ageusia) on any given day after starting study treatment by age analysis group. Compared using Fisher’s exact text. * p < 0.05.
Figure 8
Figure 8
Proportion of participants with (a) loss of sense of smell (anosmia), (b) loss of sense of taste (ageusia) and (c) loss of sense of smell (anosmia) and/or taste (ageusia) on any given day after starting study treatment by age analysis group. Compared using Fisher’s exact text. * p < 0.05.
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