High-throughput screening studies identified Abl kinase inhibitors (including imatinib) as
inhibitors of coronaviruses SARS and MERS. The SARS-CoV-2 coronavirus depend on Abl2 kinase
activity to fuse and enter into the cells. Pharmacokinetic studies demonstrated that IC50 of
imatinib for ABL1, BCR-ABL1 and ABL2 kinase inhibition is less than 1 microM (around 0.3
microM) below the expected trough plasmatic concentrations of imatinib 400 mg/day (1.7
microM). The EC50 of imatinib for the inhibition of the virus is under investigation but we
now have a first estimates with EC50 close to 2.5 microM. This plasmatic concentration is
achievable with imatinib 800 mg/d. We hypothesize that clinically achievable imatinib
concentration will block the first round of cell to cell virus infection and therefore stop
or prevent from SARS-CoV-2 infection in human. Based on our 20 years' experience of
prescribing imatinib in patients, we expect that most of the adverse events and
pharmacological interactions of imatinib can be anticipated and corrected. The eligible
population will be aged (>70y) patients hospitalized for a non-severe COVID-19 disease for
less than 7 days. Patients will be randomized 1/1 between standard of care and imatinib 800
mg per day during 14 days. The primary endpoint will be the death rate by 30 days. Secondary
endpoint will include progression to severe CIVID-19 disease, safety, outcome at 3 months. We
plan to randomize 90 patients in order to show a 10% benefit in term of death rate reduction
from 16% to 6%.