Development of Impentri, an intravenous imatinib formulation for Covid-19 acute respiratory distress syndrome (ARDS).

The accumulation of fluid in the lungs is a significant feature of the pathology in patients with severe Covid-19 infection. This build up of fluid, contributes to difficulty in breathing and in some cases death. This fluid in the lungs results in part from direct damage to cilia and mucus cells and resulting debris and in part due to plasma extravasation triggered by the immune response to infection and associated damage. Imatinib, a generic marketed drug has been shown to reduce plasma extravasation following inflammatory challenge in animal models and this effect is supported by anecdotal observations in the clinic. This project proposes to rapidly implement a multi-center, randomized, open label, double-blind, Phase IIb study to evaluate the efficacy, safety and pharmacokinetics of imatinib mesilate in patients with corona-virus associated pneumonitis. 100 patients entering ICU with a diagnosis of corona-virus associated pneumonitis will be randomised, half receiving i.v. imatinob , 200mg bid for 5 days and one half placebo. Adverse events, immunological parameters and imatinib pharmacokineticswill be monitored. Outcome measures Primary: PaO2/FiO2 ratio. Secondary: rate of intubation/need for mechanical ventilation, pulmonary edema on high resolution CT, Oxygenation Index, respiratory mechanics, duration of mechanical ventilation, fluid balance, ICU length of stay, mortality. This project has already received EMA scientific advice for the treatment of acute respirator y distress syndrome and has granted orphan drug status.