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

Original: Lancet November12, 2020

Author(s): Monk PD, Marsden RJ, Tear VJ et al.

Respiratory digests
Respiratory infections

Reviewer: Stylianos Loukides, e-Learning Director

Published: 14 Nov, 2020

SARS COV 2 infection is characterized by a wide spectrum of clinical manifestations ranging from asymptomatic or/and mild disease to severe and life threatening illness. The illness is lacking of an ideal treatment strategy. Many efforts are running in terms of an effective and safe treatment development.

The type I interferon (interferon-β) is one of the major cytokines that drive innate immune responses. SARS-CoV-2 directly suppresses the release of interferon-β in vitro and patients with severe COVID-19 infection showed decreased levels of interferon activity.

The current study aimed to determine the safety and efficacy of inhaled nebulised interferon beta-1a in patients with SARS COV 2 infection. The study was a phase 2 randomized, double-blind, placebo-controlled, multicentre study. The study population consisted of adults admitted to hospital with COVID-19 symptoms and a positive RT-PCR or point-of-care test. Inhaled SNG001 was administered once daily for 14 days with a 28 days post period follow up.

116 were initially screened and 101 were finally enrolled. 50 randomized in the SNG001 group and 51 in the placebo group. Of these, 48 patients received SNG001 and 50 received placebo, and were included in the intention-to-treat population.

The primary outcome was a change in a WHO based Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention to treat population. As secondary outcomes, change in a respiratory symptoms score, safety and tolerability of the investigational drug were assessed.

Patients receiving SNG001 had greater probability of improvement in terms of the 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). As for the secondary outcomes no significant differences were observed in terms of intubation or/and time to intubation. Recovery data showed that on day 28 patients received SNG001 were recovered in a greater proportion compared to those received placebo. Hospital discharge was not significantly differed within groups. For the symptoms based score only dyspnea was significantly improved in favor of SNG001 group.

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.

###Comments:
The study is interesting and promising. I have some concerns regarding the pre-defined outcomes and particularly the primary one, since OSCI is lacking validity in randomized trials. The size is limited and inadequate for drawing strong conclusions. But on the other hand it is a phase 2 trial where safety and tolerability are the predominant parameters. The lower number of deaths is a promising finding. What we need to further know? The applicability of the results in a larger study with similar design and stronger outcomes.