One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019: A Randomized Controlled Phase 2 Trial.

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.

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [e-mail].

Déclaration de conflit d'intérêts

Potential conflicts of interest . N. J.: research funding to the institution from Sagent Pharmaceuticals as Principal Investigator of a phase II trial (CAMELOT). K. W. C.: research funding to the institution from Merck, Sharp & Dohme, consultant fees to the author from Pardes Biosciences, honoraria from the International Antiviral Society (IAS)–USA for presentations; K.W.C. also reports serving as Chair of a Safety Monitoring Committee for an investigator-initiated study through the University of California San Francisco (UCSF). E. S. D.: receives consulting fees from Gilead Sciences, Merck, Theratechnologies, and GSK/ViiV and research support through the institution from Gilead Sciences and GSK/ViiV. D. A. W.: has received funding to the institution to support research and honoraria for advisory boards and consulting from Gilead Sciences. D. A. W. also reports grants or contracts from Eli Lilly and Merck. P. A. H.: received research funding from the National Institutes of Health (NIH) and consulting fees paid to the institution from Sagent Pharmaceuticals. A. L. G.: reports contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen, and Hologic and research support from the Bill and Melinda Gates Foundation, Gilead, and Merck, outside of the described work. J. J. E.: reports institutional research funding from Gilead Sciences; is an ad hoc consultant to GSK/Vir Biotechnology, Gilead Sciences, and Merck; and Data Monitoring Committee (DMC) Chair for Invivyd (formerly Adagio) phase III studies. J. S. C.: has consulted for Merck and Company's advisory board. D. M. S.: has consulted for the following companies: Fluxergy, Kiadis, Linear Therapies, Evidera, VxBiosciences, Model Medicines, Bayer Pharmaceuticals, Lucira, and Pharma Holdings. D. M. S. also reports honoraria for presentations or speaking engagements from IAS USA, and stock options from Fluxergy, Linear Therapies, and Model Medicines. J. Z. L.: has consulted for AbbVie and reports grants or contracts from Merck. C. M.: reports unpaid participation on the BONE STAR Data and Safety Monitoring Board (DSMB). M. D. H.: reports NIH research and training grants related to infectious diseases (paid to institution); travel support as an invited speaker at the Conference on Retroviruses and Opportunistic Infections (CROI 2023); unpaid participation in a COVID-related data committee for World Health Organization; board membership (as part of employment with Harvard) on the Botswana Harvard Partnership; and miscellaneous interests via their spouse's research grants from NIH. A. J. was an employee and B. S. is an employee of Sagent Pharmaceuticals. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.