Phase 3, multicentre, double-blind, randomised, parallel-group, placebo-controlled study of camostat mesilate (FOY-305) for the treatment of COVID-19 (CANDLE study)

Abstract

Background: In vitro drug-screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). Methods: This was a phase 3, multicentre, double-blind, randomised, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. Findings: One-hundred and fifty-five patients were randomised to receive camostat mesilate (n=78) or placebo (n=77). The median time to the first test was 11 days in both groups, and conversion to negative status was observed in 60.8% and 63.5% of patients in the camostat mesilate and placebo groups, respectively. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. Interpretation: Camostat mesilate is no more effective, based on upper airway viral clearance, than placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. Funding: Ono Pharmaceutical Co., Ltd.

Tissue‐ and cell‐expression of druggable host proteins provide insights into repurposing drugs for COVID‐19

“…up to 14 days failed in patients with COVID‐19 in a phase III, double‐blind, randomized, parallel‐group study (camostat mesylate group, n = 78; and placebo group, n = 77). 67 It remains unclear why the effects observed in preclinical studies could not be replicated in a clinical setting. One possible reason could be that, even though camostat mesylate can reach the effective level in plasma, its concentrations in the lungs might be in the subtherapeutic range.…”

“…However, treatment with oral camostat mesylate at this dose (600 mg q.i.d.) up to 14 days failed in patients with COVID‐19 in a phase III, double‐blind, randomized, parallel‐group study (camostat mesylate group, n = 78; and placebo group, n = 77) 67 . It remains unclear why the effects observed in preclinical studies could not be replicated in a clinical setting.…”