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

Monk, Phillip D.; Brookes, Jody L.; Tear, Victoria J.; Batten, Toby N.; Newall, Clare; Mankowski, Marcin; Crooks, Michael G.; Singh, Dave; Chaudhuri, Rekha; Leaker, Brian; Lunn, Kerry; Reynolds, Sophie; Dudley, Sarah; Gabbay, Felicity J.; Holgate, Stephen T.; Djukanovic, Ratko; Wilkinson, Thomas M.A.

Abstract

Background: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β 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-β1a (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.

Citation

Monk, P. D., Brookes, J. L., Tear, V. J., Batten, T. N., Newall, C., Mankowski, M., Crooks, M. G., Singh, D., Chaudhuri, R., Leaker, B., Lunn, K., Reynolds, S., Dudley, S., Gabbay, F. J., Holgate, S. T., Djukanovic, R., & Wilkinson, T. M. (2024). Nebulised interferon beta-1a (SNG001) in the treatment of viral exacerbations of COPD. Respiratory Research, 25(1), Article 228. https://doi.org/10.1186/s12931-024-02854-7

• Journal Article Type: Article
• Acceptance Date: May 17, 2024
• Online Publication Date: May 29, 2024
• Publication Date: Dec 1, 2024
• Deposit Date: Oct 15, 2024
• Publicly Available Date: Oct 18, 2024
• Journal: Respiratory Research
• Print ISSN: 1465-9921
• Electronic ISSN: 1465-993X
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 1
• Article Number: 228
• DOI: https://doi.org/10.1186/s12931-024-02854-7
• Keywords: Chronic obstructive pulmonary disease; Symptom flare up; Interferons; Biomarkers
• Public URL: https://hull-repository.worktribe.com/output/4710550