Antiviral biomarkers are upregulated in sputum cells following administration of inhaled interferon beta to COPD patients

Reynolds, Sarah J.; Lunn, Kerry; Beegan, Rona; Tear, Victoria; Monk, Phillip

doi:10.1183/13993003.congress-2019.oa263

Cited by 4 publications

(7 citation statements)

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Section: Introductionmentioning

confidence: 99%

“…11,13 In these patients, SNG001 has been shown to boost lung antiviral defences, as assessed by sputum cell antiviral biomarkers, in patients with and without respiratory viral infections. 11,14 In two phase 2 trials, SNG001 had a significantly greater beneficial effect on lung function than placebo in patients with asthma who had symptoms of respiratory viral infection. 11,15 The existing clinical data for inhaled SNG001, coupled with the known suppression of interferon-β by SARS-CoV-2, provided the rationale for a randomised, double-blind, placebo-controlled, phase 2 pilot trial to determine whether inhaled SNG001 has the potential to reduce the severity of lower respiratory tract illness and accelerate recovery in patients diagnosed with COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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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

Monk

Marsden

Tear

et al. 2021

The Lancet Respiratory Medicine

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354

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Monk

Marsden

Tear

et al. 2021

The Lancet Respiratory Medicine

Self Cite

398

354

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“…The study was not powered to evaluate the three key secondary endpoints related to disease progression, but, although not reaching statistical significance, trends favouring the addition of SNG001 to SoC were observed for each of these measures, including a 26% relative risk reduction in patients progressing to severe disease or death in the SNG001 plus SoC group compared with placebo plus SoC. Furthermore, consistent with previous clinical studies, including those in patients with asthma or COPD [19][20][21], SNG001 was well tolerated and had a favourable safety profile.…”

Section: Discussionmentioning

confidence: 55%

“…The aim of delivery via nebuliser is to achieve a high local concentration within the lower respiratory tract, the site of SARS-CoV-2 infection [18]. Inhaled SNG001 has been shown to upregulate antiviral biomarker levels in the lungs of patients with chronic obstructive pulmonary disease (COPD) or asthma [19][20][21], and to have potent in-vitro antiviral activity against SARS-CoV-2, including a number of variants of concern [22].…”

Section: Introductionmentioning

confidence: 99%

Nebulised interferon-β1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study

et al. 2022

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BackgroundDespite the availability of vaccines and therapies, patients are being hospitalised with COVID-19. Interferon-β is a naturally-occurring protein that stimulates host immune responses against most viruses, including SARS-CoV-2. SNG001 is a recombinant interferon-β1a formulation delivered to the lungsvianebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygenvianasal prongs or mask.MethodsPatients 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 SNG001versusplacebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary endpoints were: progression to severe disease or death; progression to intubation or death; and death.ResultsMedian time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio 1.06 [95%CI 0.89, 1.27]; p=0.51); time to recovery was 25.0 days in both groups (1.02 [0.81, 1.28]; p=0.89). There were no significant SNG001–placebo differences for the key secondary endpoints, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; odds ratio 0.71 [0.44, 1.15]; p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively.ConclusionsAlthough the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary endpoints analysis suggested that SNG001 may have prevented progression to severe disease.Study registration number: ISRCTN85436698

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“…In addition, given that EVs have been shown to modulate the IFN response, they may have useful anti-viral therapeutic applications. The potential of IFN treatment in the prevention of virally induced exacerbations in COPD is currently being investigated ( 131 , 132 ).…”

Section: Respiratory Infections Inflammation and The Development Of Chronic Diseasementioning

confidence: 99%

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

et al. 2021

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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

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Antiviral biomarkers are upregulated in sputum cells following administration of inhaled interferon beta to COPD patients

Cited by 4 publications

References 0 publications

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

Nebulised interferon-β1a (SNG001) in hospitalised COVID-19: SPRINTER phase III study

The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

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