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.

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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Background People with post-COVID conditions can have a wide range of symptoms lasting months and it can affect as many as one in five infected people. Interferon beta (IFN-β) is key in host defence against viruses but can be suppressed by virus or host factors locally at the site of infection. Inhalation of SNG001 (IFN-β-1a nebuliser solution) aims to restore lung IFN-β levels. SPRINTER (NCT04732949) was a RCT of inhaled interferon beta in hospitalised COVID-19. There was no effect of SNG001 on the primary endpoints of time to discharge or recovery most likely due to improvements in the standard of care. However, there was an encouraging signal for the key secondary endpoint of prevention of progression to severe disease or death (ITT 26% relative risk reduction [RRR]; Odds Ratio [95% CI]: 0.71 [0.44, 1.15]; Per Protocol 36% RRR; OR 0.63 [0.35, 1.13]). Post hoc analyses showed enhanced effects favouring SNG001 in subgroups at higher risk of progression. We report on the impact of SNG001 on long COVID symptoms in SPRINTER. Methods Patients requiring low-flow oxygen were randomized to receive SNG001 (314) or placebo (309) once daily for 14 days, plus standard-of-care. Long COVID symptoms were assessed as a secondary endpoint at follow-up visits via telephone/video call on Day 60 and Day 90. The following patient reported outcome (PRO) measures were also assessed: General Anxiety Disorder 7 Questionnaire (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale and Brief Pain Inventory (Short Form). Results When compared to placebo, SNG001 reduced the relative risk of common symptoms of long COVID (fatigue/malaise [RRR=35.4%]; dyspnoea [RRR=28.3%]; loss of smell and/or taste [RRR=61.4%]). Analysis of the PROs is ongoing. Assessment of COVID symptoms at Day 60 and 90 follow up visits Effect of SNG001 treatment on long COVID symptoms Conclusion Long COVID can leave patients with lingering cognitive, respiratory, and functional symptoms months after a SARS-CoV-2 infection. Given the shift from pandemic to endemic status for COVID-19 and the need for new treatments then these findings, suggesting SNG001 may be impacting common long COVID symptoms, provide additional support for the further investigation of SNG001. Disclosures Phillip D. Monk, PhD, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Board Member|Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Victoria J. Tear, PhD, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Jody L. Brookes, BSc, Synairgen Plc (Employed by Synairgen Research Ltd which is a subsidiary of Synairgen Plc, Stocks/Bonds): Stocks/Bonds Marcin Mankowski, MD, MFPM (Dis), CytoDyn: Advisor/Consultant|Entasis: Advisor/Consultant|ImmuPharma: Advisor/Consultant|Menarini: Advisor/Consultant|Pfizer: Advisor/Consultant|Synairgen: Advisor/Consultant|Venatorx: Advisor/Consultant Ratko Djukanovic, MD, Synairgen: Advisor/Consultant|Synairgen: Honoraria|Synairgen: Stocks/Bonds Stephen T. Holgate, FMedSci, MD, Synairgen: Board Member|Synairgen: Non executive board director, patent on inhaled interferon beta|Synairgen: Stocks/Bonds chris brightling, FMedSci, Synairgen: Advisor/Consultant|Synairgen: Grant/Research Support Tom Wilkinson, PhD, PhD, AZ: Grant/Research Support|AZ: Honoraria|My mhealth: Board Member|My mhealth: Ownership Interest|My mhealth: Stocks/Bonds|Synairgen: Grant/Research Support|Synairgen: Honoraria.