Phase I Clinical Trial. Safety of Baricitinib to prevent respiratory insufficiency in oncohematological patients affected by Coronavirus Disease-19: BARCOVID19 study

Abstract

Abstract Background Oncohematological patients, due to their secondary immunodeficiency, are at a higher risk of mortality related to COVID-19 infection. Baricitinib, a JAK2 inhibitor, has a dual effect in this context, reducing the inflammatory response to the virus and diminishing virus endocytosis. Methods This phase I safety run-in cohort study aimed to determine the dose-limiting toxicity of baricitinib in terms of the rate of serious events in oncohematological patients with COVID-19. The drug was administered on an inpatient basis at an oral dose of 4 mg daily for 5 to 7 days, associated with the institutional standard of care (SOC). Results Six patients with solid tumors or hematological malignancies were enrolled in the study. Sixty percent of the patients received active anticancer treatment at the time of inclusion. Lymphopenia and elevation of acute-phase reactants were the most frequent laboratory findings that improved during the treatment course. All patients received corticosteroids, but only 3 of them received remdesivir as the SOC. The most common adverse events were bacterial infections, including pneumonia, urinary tract infections, and bacteremia. The mortality rate due to disease progression and respiratory insufficiency is 33%. The severe adverse event rate was less than 33%, with no adverse events or mortality caused by baricitinib. Conclusions The results of the present study demonstrate that baricitinib is a safe treatment for patients with oncohematological diseases and COVID-19. However, its efficacy and superiority to standard treatment will require further testing in phases 2 and 3 trials. Trial registration: AEMPs: 20–0356 EudraCT: 2020-001789-12