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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

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
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

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. Funding: Synairgen Research.

2213-2600
196-206
Monk, Phillip D
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Marsden, Richard J
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Tear, Victoria J
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Brookes, Jody
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Batten, Toby N
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Mankowski, Marcin
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Gabbay, Felicity J
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Davies, Donna E
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Horsley, Alexander
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Monk, Phillip D
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Marsden, Richard J
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Tear, Victoria J
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Brookes, Jody
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Harrison, Timothy W
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Saralaya, Dinesh
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Beegan, Rona
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Thompson, Angela
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Monk, Phillip D, Marsden, Richard J, Tear, Victoria J, Brookes, Jody, Batten, Toby N, Mankowski, Marcin, Gabbay, Felicity J, Davies, Donna E, Holgate, Stephen T, Ho, Ling-pei, Clark, Tristan, Djukanovic, Ratko, Wilkinson, Tom M.A., Crooks, Michael G, Dosanjh, Davinder Ps, Siddiqui, Salman, Rahman, Najib M, Smith, Jacklyn A, Horsley, Alexander, Harrison, Timothy W, Saralaya, Dinesh, Mcgarvey, Lorcan, Watson, Alastair, Foster, Edmund, Fleet, Adam, Singh, Dave, Hemmings, Sophie, Aitken, Sandra, Dudley, Sarah, Beegan, Rona, Thompson, Angela and Rodrigues, Pedro Mb (2020) 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. The Lancet Respiratory Medicine, 9 (2), 196-206. (doi:10.1016/S2213-2600(20)30511-7).

Record type: Article

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. Funding: Synairgen Research.

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Accepted/In Press date: 19 October 2020
Published date: 1 November 2020

Identifiers

Local EPrints ID: 445094
URI: http://eprints.soton.ac.uk/id/eprint/445094
ISSN: 2213-2600
PURE UUID: b2b7a24e-4259-4399-9f95-ee5b5de422c6
ORCID for Donna E Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Tristan Clark: ORCID iD orcid.org/0000-0001-6026-5295
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 19 Nov 2020 17:32
Last modified: 20 Feb 2021 02:45

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Contributors

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 ORCID iD
Author: Ling-pei Ho
Author: Tristan Clark ORCID iD
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

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