A randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19.

We performed a pilot study of upamostat, a serine protease inhibitor, in outpatients with symptomatic COVID-19 before a pivotal trial. SARS-CoV-2 patients with ≥2 moderate-severe symptoms onset within 5 days were randomized to oral upamostat 200 or 400 mg or placebo daily for 14 days. Patients completed COVID-19 symptom questionnaires daily for 28 days, then thrice weekly for 4 weeks, and underwent physical and laboratory examinations periodically. A total of 61 patients enrolled of which 20 received a placebo or upamostat 200 mg daily; 21 received upamostat 400 mg daily. Treatment was well tolerated; only one patient (upamostat 400) reported a drug-related adverse event, mild skin rash; no patient discontinued owing to a drug-related adverse event. The median time to a sustained recovery from severe symptoms was 8, 4, and 3 days for the three treatment groups, respectively. New severe symptoms developed in 20% of the placebo group vs 2.4% in the combined upamostat groups, (P = 0.036). Three placebo patients (15%) versus no upamostat patients were hospitalized for worsening COVID (P= 0.03). The mean d-dimer level remained constant in placebo patients but decreased by 38% and 48% in upamostat 200 and 400 patients, respectively. Upamostat was well tolerated, shortened recovery time, and decreased new severe symptoms and hospitalization.

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Déclaration de conflit d'intérêts

Declaration of competing interest Drs. Plasse, Abramson, and Fathi, and Ms. Fehrmann were contractors to RedHill Biopharma, Ltd, the sponsor of the study. Drs. Delgado, Potts, and McComsey were investigators whose organizations or institutions were paid by the sponsor to conduct the study.