Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD.

BACKGROUND: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-ß is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-ß1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. METHODS: In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). RESULTS: In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001-placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. CONCLUSIONS: Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. TRIAL REGISTRATION: EU clinical trials register (2017-003679-75), 6 October 2017.

Feasibility of home administration of nebulised interferon ß-1a (SNG001) for COVID-19: a remote study.

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-ß1a (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.

Nebulised interferon-ß1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study.

Background: Despite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-ß 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-ß1a 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.