Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: a randomized placebo-controlled phase II trial

Els Tobback, Sophie Degroote, Sabine Buysse, Liesbeth Delesie, Lucas Van Dooren, Sophie Vanherrewege, Cyril Barbezange, Veronik Hutse, Marta Romano, Isabelle Thomas, Elizaveta Padalko, Steven Callens, Marie-Angélique De Scheerder, Els Tobback, Sophie Degroote, Sabine Buysse, Liesbeth Delesie, Lucas Van Dooren, Sophie Vanherrewege, Cyril Barbezange, Veronik Hutse, Marta Romano, Isabelle Thomas, Elizaveta Padalko, Steven Callens, Marie-Angélique De Scheerder

Abstract

Objectives: This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting.

Methods: We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo. Outcomes included change in nasopharyngeal viral load, time to clinical improvement, the presence of neutralizing antibodies, and safety.

Results: Of 96 participants randomized between November 2020 and June 2021, analyses were performed on the data of 90 participants who completed treatment (N = 61 camostat mesylate, N = 29 placebo). The estimated mean change in cycle threshold between day 1 and day 5 between the camostat and placebo group was 1.183 (P = 0.511). The unadjusted hazard ratio for clinical improvement in the camostat group was 0.965 (95% confidence interval, 0.480-1.942, P = 0.921 by Cox regression). The percentage distribution of the 50% neutralizing antibody titer at day 28 visit and frequency of adverse events were similar between the two groups.

Conclusion: Under this protocol, camostat mesylate was not found to be effective as an antiviral drug against SARS-CoV-2.

Trial registration: ClinicalTrials.gov NCT04625114; November 12, 2020.

Keywords: COVID-19; Camostat; Efficacy; Neutralizing antibodies; Randomized controlled trial; Safety.

Conflict of interest statement

Conflict of interest The authors have no conflicts of interest to declare.

Copyright © 2022. Published by Elsevier Ltd.

Figures

Figure 1
Figure 1
Flow diagram
Figure 2
Figure 2
Polymerase chain reaction (PCR) cycle threshold (Ct) values at baseline (V1) and day five visit (V5). Each data point represents the Ct value from one patient in the camostat mesylate versus the placebo group. A lower Ct value corresponds to a higher viral load.
Figure 3
Figure 3
Kaplan-Meier curve for time to clinical improvement
Figure 4
Figure 4
Distribution of 50% neutralizing antibody titer (NT50, reciprocal serum dilution) of participants treated with camostat mesylate (blue) and placebo (red). The NT50 value of 40 is the detection limit, and values determined to be less than 40 are treated as 40.

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