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

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.

Figure 1

Trial profile Eligible patients were randomly assigned (1:1) to receive inhaled nebulised interferon beta-1a (SNG001) or placebo. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.

Figure 2

Odds ratios of recovery (OSCI ≤1), hospital discharge, and improvement Odds ratios of recovery (defined as unchanged post-baseline OSCI score of 0 or 1), hospital discharge, and improvement on the WHO OSCI on days 15 or 16 (end-of-treatment visit) and on day 28 (follow-up visit) are shown. Comparisons were made between the SNG001 group (n=48) and placebo group (n=50) in the intention-to-treat population. OSCI=Ordinal Scale for Clinical Improvement.

Figure 3

Patient recovery (OSCI ≤1) during the study The proportion of patients who recovered (defined as having an unchanged post-baseline OSCI score of 0 or 1) up to day 15 or 16 (end-of-treatment visit) and on day 28 (follow-up visit) is presented for the intention-to-treat population (SNG001: n=48; placebo: n=50). OSCI=Ordinal Scale for Clinical Improvement.

Figure 4

Hospital discharge The proportion of patients who were discharged from hospital up to day 15 or 16 (end-of-treatment visit) and on day 28 (follow-up visit) is presented for the intention-to-treat population (SNG001: n=48; placebo: n=50).

Figure 5

Breathlessness, Cough, and Sputum Scale evaluation Least squares mean (95% CI) change from the baseline score up to day 14 is presented for total BCSS scores (A) and individual scores for breathlessness (B), cough (C), and sputum (D) for the intention-to-treat population (SNG001: n=48; placebo: n=50). BCSS=Breathlessness, Cough, and Sputum Scale.