Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial

Type Journal Article Author Phillip D. Monk Author Richard J. Marsden Author Victoria J. Tear Author Jody Brookes Author Toby N. Batten Author Marcin Mankowski Author Felicity J. Gabbay Author Donna E. Davies Author Stephen T. Holgate Author Ling-Pei Ho Author Tristan Clark Author Ratko Djukanovic Author Tom M. A. Wilkinson Author Michael G. Crooks Author Davinder PS Dosanjh Author Salman Siddiqui Author Najib M. Rahman Author Jacklyn A. Smith Author Alexander Horsley Author Timothy W. Harrison Author Dinesh Saralaya Author Lorcan McGarvey Author Alastair Watson Author Edmund Foster Author Adam Fleet Author Dave Singh Author Sophie Hemmings Author Sandra Aitken Author Sarah Dudley Author Rona Beegan Author Angela Thompson Author Pedro MB Rodrigues URL https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30511-7/abstract Publication The Lancet Respiratory Medicine ISSN 2213-2600, 2213-2619 Date 12/11/2020 Extra Publisher: Elsevier PMID: 33189161 Journal Abbr The Lancet Respiratory Medicine DOI 10.1016/S2213-2600(20)30511-7 Library Catalog www.thelancet.com Language English Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. Methods We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov (NCT04385095); the pilot trial of inpatients with COVID-19 is now completed. Findings Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 [95% CI 1·07–5·04]; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 [95% CI 1·03–4·69]; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven [15%] patients in the SNG001 group and five [10%] in the placebo group). There were three deaths in the placebo group and none in the SNG001 group. Interpretation Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials. Short Title Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection