Ozanimod therapy in COVID-19 patients requiring oxygen support: a randomized, open label, pilot trial

Sphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathologic damages in models of viral pneumonia.Is it feasible to administer an SRL therapy, here ozanimod (OZA), to acutely ill patients infected with SARS-CoV-2?The prospective, randomized, open-label, COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care (SOC) or to SOC plus OZA. OZA (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary end point investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the World Health Organization-adapted six-point ordinal scale for clinical improvement analyzed under the intention-to-treat principle.Twenty-three patients were randomized to the SOC arm, and 20 were randomized to the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed nonsignificant reductions of median duration of respiratory support (6 [range, 3-10] vs 9 [range, 4-12] days; P = .34), median duration of hospitalization (9 [range, 6-12] vs 10 [range, 6-18] days; P = .20), and median time to clinical improvement (4 [range, 3-7] vs 7 [range, 3-11] days; P = .12) for OZA compared with SOC, respectively. Heart rate was significantly lower with OZA (65 [range, 63-67] vs 71 [range, 69-72] beats/min; P < .0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported.To our knowledge, SRL utility in severe pneumonia has never been tested in patients. We show for the first time that this new pharmacologic agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated.ClinicalTrials.gov; No.: NCT04405102; URL: www.gov.