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Background: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic. Aim: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-β1a (SNG001) in this setting. Design & setting: Randomised, double-blind, parallel-group study, which was conducted remotely. Method: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely. Results: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related. Conclusion: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-β is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-β1a formulation delivered to the lungs via nebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygen via nasal prongs or mask., Methods: Patients were randomised double-blind to SNG001 (n=309) or placebo (n=314) once daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001 versus placebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary end-points were progression to severe disease or death, progression to intubation or death and death., Results: Median time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio (HR) 1.06 (95% CI 0.89-1.27); p=0.51); time to recovery was 25.0 days in both groups (HR 1.02 (95% CI 0.81-1.28); p=0.89). There were no significant SNG001-placebo differences for the key secondary end-points, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; OR 0.71 (95% CI 0.44-1.15); p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively., Conclusions: Although the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary end-points analysis suggested that SNG001 may have prevented progression to severe disease., Competing Interests: This study is registered at the ISRCTN registry with identifier number ISRCTN85436698. The data analysed and presented in this study are available from the corresponding author on reasonable request, providing the request meets local ethical and research governance criteria after publication. Patient-level data will be anonymised and study documents will be redacted to protect the privacy of trial participants. Conflict of interest: In addition to the writing support declared above, the authors have the following conflicts of interest to declare. P.D. Monk is an employee of Synairgen Research plc, the parent company of Synairgen Research Ltd (and such costs are met by Synairgen Research Ltd), the sponsor of this trial, and owns shares and has options on shares in Synairgen plc. J.L. Brookes is an employee of Synairgen Research Ltd, the sponsor of this trial, and has options on shares in Synairgen plc. V.J. Tear is an employee of Synairgen Research Ltd, the sponsor of this trial, and owns shares and has options on shares in Synairgen plc. T.N. Batten provided statistical support, programming and consultancy to Synairgen Research Ltd via a contract with his employer, Veramed Ltd. M. Mankowski provided consulting services to Synairgen Research Ltd, the sponsor of this trial, with all payments made to tranScrip Ltd. T. Adzic-Vukicevic has no other conflicts of interest to disclose. M.G. Crooks has no other conflicts of interest to disclose. D.P.S. Dosanjh declares grants from GlaxoSmithKline (Supported Studies Programme) and Birmingham Health Partners CARP Fellowship, honorarium for meeting and podcast from Boehringer Ingelheim, support to attend congresses from Boehringer Ingelheim (no payment received), patent 0406271.7, filed 21 March 2005 (Mycobacterium tuberculosis infection diagnostic text), and participation in a data safety monitoring board or advisory board from AstraZeneca, Boehringer Ingelheim and the HAP-FAST trial, all outside the scope of this manuscript. M. Kraft declares the receipt of funding to her institution from Synairgen Research Ltd, the sponsor of this trial. Outside the scope of the trial she declares funds paid to her institution from the National Institutes of Health, American Lung Association, Sanofi-Regeneron and AstraZeneca, consulting fees from AstraZeneca, Sanofi-Regeneron and Genentech, one patent issued and one pending for which she received no funds directly (she is Chief Medical Officer and Co-founder of RaeSedo, Inc.), funds for the participation in a data safety monitoring board for the ALUND Study, funds for a leadership role of the National Heart, Lung and Blood Scientific Advisory Council (NIH), and the future receipt of stock options in RaeSedo, Inc. C.E. Brightling declares grants and consulting fees paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic and 4DPharma, all outside the scope of this manuscript. F.J. Gabbay declares the receipt of consulting fees paid to tranScrip Ltd from Synairgen Research plc, the sponsor of this trial, and participation in a data safety monitoring board for Synairgen. She is also president of the Faculty of Pharmaceutical Medicine of the UK Royal College of Physicians. S.T. Holgate received payments as nonexecutive director of, and owns shares in, Synairgen plc, the parent company of the sponsor of this trial. R. Djukanovic declares the receipt of consulting fees and payment for participation in a data safety monitoring board or advisory board from Synairgen Research Ltd, the sponsor of this trial; and owns shares in Synairgen plc, the parent company of the sponsor of this trial. Outside the trial, he declares payment or honoraria from Regeneron, GlaxoSmithKline and Kymab. T.M.A. Wilkinson received research funding and consultancy fees from Synairgen Research Ltd, the sponsor of this trial. Outside the trial, he declares research grants from the National Institute for Health and Care Research, Medical Research Council, Bergenbio, AstraZeneca, UCB and Janssen, consultancy fees from AstraZeneca, Valneva, Olam Pharma, Janssen and My mHealth, lecture fees from AstraZeneca, Boehringer Ingelheim and Roche, participation on a data safety monitoring board for Valneva, and that he holds stock in My mHealth., (Copyright ©The authors 2023.)