Safety and efficacy of inhaled interferon-β1a (SNG001) in adults with mild-to-moderate COVID-19: a randomized, controlled, phase II trial

Abstract

Background: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.

Methods: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021.

Findings: The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm.

Interpretation: In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia.

Funding: The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords: ACTIV-2; COVID-19; Inhaled interferon; Randomized clinical trial; SARS-CoV-2.

Fig. 1

Consort diagram. The modified intent-to-treat (mITT) population consists of 220 participants who received at least one dose of study treatment, including 110 who received SNG001, 52 who received placebo for SNG001, and 58 who were eligible to receive SNG001 but were allocated to another phase 2 placebo. One additional participant was allocated to placebo for SNG001 but did not initiate treatment.

Fig. 2

Time (days) to all targeted symptoms improved from day 0 for two consecutive days. The primary clinical outcome was time to symptom improvement through 28 days of 13 targeted COVID-19 symptoms. The cumulative proportion of participants with all symptoms improved for 2 consecutive days was calculated using Kaplan–Meier methods. Numbers above the x-axis indicates the number of participants still in follow-up who have not previously had two consecutive days with all targeted symptoms improved.

Fig. 3

Cumulative incidence of hospitalization or death through day 28. Cumulative incidence of hospitalization or death is estimated by Kaplan–Meier method. Hospitalization is defined as ≥24 h of acute care, in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe COVID-19 during the COVID-19 pandemic, through day 28. There were no deaths through day 28. Numbers above the x-axis indicates the number of participants still in follow-up who have not been hospitalized or died.

Fig. 4

SARS-CoV-2 RNA levels from nasopharyngeal swabs by study visit. (A) The primary virologic outcome was proportion of participants with SARS-CoV-2 RNA below lower limit of quantification (LLoQ) from nasopharyngeal (NP) swabs at days 3, 7, and 14 between participants randomized to SNG001 and placebo. (B) Comparison of SARS-CoV-2 RNA levels between participants randomized to SNG001 or placebo at study entry and days 3, 7, 14, and 28, with horizontal line = median, box = interquartile range, whiskers = minimum/maximum. SARSCoV-2 RNA was measured using a quantitative Abbott m2000sp/rt platform with a limit of detection (LOD) of 1.4 log₁₀ copies/mL, lower limit of quantification (LLoQ) of 2 log₁₀ copies/mL, and upper limit of quantification (ULoQ) of initially 7, then 8 log₁₀ copies/mL.