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

Inhaled Interferon Beta COVID-19 Study Group

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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.

Original languageEnglish
Pages (from-to)196-206
Number of pages11
JournalThe Lancet Respiratory Medicine
Volume9
Issue number2
DOIs
Publication statusPublished - 12 Nov 2020

Bibliographical note

Funding Information:
This study was funded by Synairgen Research, UK. TMAW is supported in part by the NIHR Southampton Biomedical Research Centre. L-PH is supported in part by the NIHR Oxford Biomedical Research Centre. We thank all patients who volunteered for the study and clinical and research teams at all the participating clinical centres and the NIHR Respiratory Translational Research Collaboration for support in trial delivery. We are grateful to Antigoni Ekonomou of Niche Science & Technology for medical writing services and editorial assistance with the manuscript. We thank also Alastair Watson for helping with the preparation of the manuscript and coordination of the submission.

Funding Information:
This study was funded by Synairgen Research, UK. TMAW is supported in part by the NIHR Southampton Biomedical Research Centre. L-PH is supported in part by the NIHR Oxford Biomedical Research Centre. We thank all patients who volunteered for the study and clinical and research teams at all the participating clinical centres and the NIHR Respiratory Translational Research Collaboration for support in trial delivery. We are grateful to Antigoni Ekonomou of Niche Science & Technology for medical writing services and editorial assistance with the manuscript. We thank also Alastair Watson for helping with the preparation of the manuscript and coordination of the submission.

Funding Information:
PDM is a Director of Synairgen Research (a University of Southampton spin-out company), is an employee and Director of Synairgen (the parent company of Synairgen Research), and own shares and holds share options in Synairgen. RJM is a Director of Synairgen Research, is an employee and Director of Synairgen, and own shares and holds share options in Synairgen. VJT is an employee of Synairgen Research and holds share options in Synairgen. PDM and VJT also have a patent (GB 2011216.5: Use of inhaled interferon-beta to improve outcome in SARS-CoV-2 infected patients) pending. JB is an employee of Synairgen Research and holds share options in Synairgen. MM reports fees as a consultant from Synairgen Research, outside of the submitted work. FJG is a Managing Partner of Transcrip Partners and reports personal fees from TranScrip Partners who supported Synairgen for the study, and personal fees from TranScrip Partners outside of this work. FJG was also a member of the independent data safety monitoring committee. DED is a co-founder of Synairgen Research, owns shares in Synairgen, and has received personal fees and other fees as a consultant to Synairgen Research during and outside of the conduct of the trial. DED has also received a grant from Boehringer Ingelheim for fibrosis studies unrelated to the trial and has patents relating to antiviral therapy for respiratory diseases (PCT/GB2005/050031) and the use of interferon-beta as a form of antiviral therapy for respiratory diseases (WO2005087253A3), with royalties paid to the University of Southampton and the inventors. STH is a co-founder of Synairgen Research, owns shares in the company, and has received personal fees as a Non-Executive Director and Consultant of Synairgen Research outside of the submitted work. STH also has patents for the use of interferon-beta as a form of antiviral therapy for respiratory diseases (WO2005087253A3 WIPO [PCT]; issued), antiviral therapy for respiratory diseases (US20090257980A1; issued), and inhaled interferon beta for COVID-19 (pending); STH is also Chair of the Academy of Medical Sciences for the report Preparing for a challenging winter 2020/21, published July 14, 2020. L-PH reports receiving funds from Synairgen Research to carry out a phase 1 clinical trial at her institution during the conduct of the study and grants from Celgene for a research study in fibrosis, outside of the submitted work. TC reports receipt of personal fees from BioMerieux and BioFire, Roche, Janssen, Cidara Therapeutics, Synairgen Research, and Randox; non-financial support from BioMerieux and BioFire, and Qiagen; and other fees from Synairgen Research outside of the submitted work. RD reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca, and Teva, consultation fees for Teva and Novartis as a member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. RD is a co-founder, current consultant, and owns shares in Synairgen Research. TMAW reports receipt of personal fees and travel support from My mHealth, grants and personal fees from GlaxoSmithKline; grants and personal fees from AstraZeneca; personal fees from Boehringer Ingelheim; and grants and personal fees from Synairgen Research, outside of the submitted work. TNB declares no competing interests.

Publisher Copyright:
© 2021 Elsevier Ltd

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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