One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial
Nikolaus Jilg, Kara W Chew, Mark J Giganti, Eric S. Daar, David A. Wohl, Arzhang Cyrus Javan, Amy Kantor, Carlee Moser, Robert W. Coombs, Gene Neytman, Keila Hoover, Atasi Jana, Phil A. Hart, Alexander L. Greninger, Bob Szurgot, Joseph J. Eron, Judith S. Currier, Michael D. Hughes, Davey M. Smith, Jonathan Z. Li, for the ACTIV-2/A5401 Study Team, Kara W Chew, David R. Smith, Eric S. Daar, David A. Wohl, Judith S. Currier, Joseph J. Eron, Arzhang Cyrus Javan, Michael D. Hughes, Carlee Moser, Mark J Giganti, Justin Ritz, Lara Hosey, Jhoanna Roa, Nilam Patel, Kelly Colsh, Irene Rwakazina, Justine Beck, Scott F. Sieg, Jonathan Z. Li, Courtney V. Fletcher, William A. Fischer, Teresa H. Evering, Robert W. Coombs, Rachel Bender Ignacio, Sandra Wagner Cardoso, Katya Corado, Prasanna Jagannathan, Nikolaus Jilg, Alan S. 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, Bob Szurgot
Abstract
BACKGROUND: Camostat inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. We studied the safety and efficacy of camostat in ACTIV-2/A5401, a phase 2/3 platform trial of therapeutics for COVID-19 in nonhospitalized adults. METHODS: We conducted a phase 2 study in adults with mild-to-moderate COVID-19 randomized to oral camostat for 7 days or a pooled placebo arm. Primary outcomes were time to improvement in COVID-19 symptoms through day 28, proportion of participants with SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) from nasopharyngeal swabs through day 14, and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. RESULTS: Of 216 participants (109 randomized to camostat, 107 to placebo) who initiated study intervention, 45% reported ≤5 days of symptoms at study entry and 26% met the protocol definition of higher risk of progression to severe COVID-19. Median age was 37 years. Median time to symptom improvement was 9 days in both arms (P = .99). There were no significant differences in the proportion of participants with SARS-CoV-2 RNA <LLoQ on days 3, 7, and 14. Through day 28, 6 (5.6%) participants in the camostat arm and 5 (4.7%) in the placebo arm were hospitalized; 1 participant in the camostat arm subsequently died. Grade ≥3 TEAEs occurred in 10.1% of camostat versus 6.5% of placebo participants (P = .35). CONCLUSIONS: In a phase 2 study of nonhospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance or time to symptom improvement, or reduce hospitalizations or deaths. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT04518410.