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

Prasanna Jagannathan; Kara W Chew; Mark J Giganti; Michael D Hughes; Carlee Moser; Mark J Main; Phillip D Monk; Arzhang Cyrus Javan; Jonathan Z Li; Courtney V Fletcher; Caitlyn McCarthy; David A Wohl; Eric S Daar; Joseph J Eron; Judith S Currier; Upinder Singh; Davey M Smith; William Fischer; ACTIV-2/A5401 Study Team

doi:10.1016/j.eclinm.2023.102250

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

EClinicalMedicine. 2023 Oct 6:65:102250. doi: 10.1016/j.eclinm.2023.102250. eCollection 2023 Nov.

Authors

Prasanna Jagannathan¹, Kara W Chew², Mark J Giganti³, Michael D Hughes³, Carlee Moser³, Mark J Main⁴, Phillip D Monk⁴, Arzhang Cyrus Javan⁵, Jonathan Z Li⁶, Courtney V Fletcher⁷, Caitlyn McCarthy³, David A Wohl⁸, Eric S Daar⁹, Joseph J Eron⁸, Judith S Currier², Upinder Singh¹, Davey M Smith¹⁰, William Fischer⁸; ACTIV-2/A5401 Study Team

Collaborators

ACTIV-2/A5401 Study Team:
Kara Chew, David Davey Smith, Eric Daar, David Wohl, Judith Currier, Joseph Eron, Arzhang Cyrus Javan, Michael Hughes, Carlee Moser, Mark Giganti, Justin Ritz, Lara Hosey, Jhoanna Roa, Nilam Patel, Kelly Colsh, Irene Rwakazina, Justine Beck, Scott Sieg, Jonathan Li, Courtney Fletcher, William Fischer, Teresa Evering, Rachel Bender Ignacio, Sandra Cardoso, Katya Corado, Prasanna Jagannathan, Nikolaus Jilg, Alan Perelson, Sandy Pillay, Cynthia Riviere, Upinder Singh, Babafemi Taiwo, Joan Gottesman, Matthew Newell, Susan Pedersen, Joan Dragavon, Cheryl Jennings, Brian Greenfelder, William Murtaugh, Jan Kosmyna, Morgan Gapara, Akbar Shahkolahi, Mark J Main, Gerald Pierone, Juliana Elliott, Jeffrey Jacobson, Leila Hojat, Julie Pasternak, Jonathan Berardi, Celine Arar, Yevgeniy Bukhman, Manish Jain, Eugene Bukhman, Sadia Shaik, Timothy Hatlen, Kelly Dooley, Becky Becker, Adaliah Wilkins, Jose Pérez, Eloy Roman, Heriberto Fernández, Keila Hoover, James Renfroe, Mauney Weldon, Genei Bougher, Carlos Malvestutto, Heather Harber, Robyn Cicarella, Gene Neytman, Jack Herman, Craig Herman, Mariam Aziz, Joan Swiatek, Divya Pathak, Madhu Choudhary, Jennifer Sullivano, Olayemi Osiyemi, Myriam Izquierdo, Odelsey Torna, Aleen Khodabakhshian, Samantha Fortier, Constance Benson, Steven Hendrickx, Rosemarie Ramirez, Anne Luetkemeyer, Suzanne Hendler, Dennis Dentoni-Lasofsky, Mario Castro, Leslie Spikes, Chase Hall, Jonathan Oakes, Amy James Loftis, Pablo Tebas, William Short, Sarah McGuffin, Chris Jonsson, Rachel Presti, Alem Haile

Affiliations

¹ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
³ Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁴ Synairgen Research Ltd, Southampton, United Kingdom.
⁵ National Institutes of Health, Bethesda, MD, USA.
⁶ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ University of Nebraska Medical Center, College of Pharmacy, USA.
⁸ Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
⁹ Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁰ Department of Medicine, University of California, San Diego, La Jolla, CA, USA.

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.

Associated data

ClinicalTrials.gov/NCT04518410

Abstract

Associated data

Grants and funding