IMPENTRI will look for clinical proof of the benefit of imatinib in COVID-19 acute respiratory distress syndrome
The build-up of fluid in the lungs is common among patients with severe cases of COVID-19 infection, and can lead to breathing problems and even death. It’s caused by the damage to cells that line the blood vessels around the lungs, and the resultant leakage of plasma into the lung itself that’s triggered by the patient’s immune response.
An existing drug called imatinib, used to treat certain types of cancer, has been shown in animal models to reduce this plasma leak, known as extravasation, caused by inflammation. This effect is also supported by anecdotal observations in the clinic.
This IMPENTRI project will carry out a randomised double-blind clinical trial to get data on the efficacy, safety and pharmacokinetics of intravenous imatinib in patients with coronavirus-associated pneumonitis. The trial will include 100 patients in the intensive care unit who have received a diagnosis of coronavirus-associated pneumonitis. Half will receive imatinib intravenously for 7 days and the other half will receive a placebo, and all will be monitored for oxygen levels, fluid balance, length of stay and other clinical outcomes.
There is already extensive safety data on the oral form of the drug. Its use to reduce plasma extravasation is novel, says David Cavalla, CEO of Exvastat. This application was discovered several years ago at the VUmc, Amsterdam.
A study involving COVID-19 patients administered with the drug in oral form is already underway in Amsterdam. “We propose to also progress and intravenous formulation for use in an intensive care setting. An intravenous formulation has been defined and final validation experiments are underway ahead of clinical manufacture for an intravenous trial later this year,” says Cavalla.
The first major milestone for the project will be an interim read-out of clinical safety for the oral therapy in September. The intravenous trial will start later this year. “Compassionate use, more widely, will be considered following completion of these studies next year in parallel with progression to phase three clinical trials,” adds Cavalla.
The project has already received scientific advice from the European Medicines Agency (EMA) for the treatment of acute respiratory distress syndrome. The EMA has granted orphan drug status.