Over the past nine months, clinical trials conducted at the University of Virginia have led to new treatments for patients fighting COVID-19 and new tools for health care workers saving lives around the commonwealth and world.
“We have been able to learn very quickly, and try new things that have changed the way we approach treatment for this virus,” said Dr. Kyle Enfield, a professor and physician in pulmonary and critical care medicine who has helped to coordinate clinical trials at UVA Health.
“We are seeing clinical research happen at a speed that has never been seen before, both for drug therapies and vaccine development,” Dr. Linda Duska, associate dean for clinical research in the School of Medicine, added. “We’ve also seen funding and the regulatory apparatus really adapt to this pandemic, while maintaining rigorous standards.”
Four clinical trials of COVID-19 drug therapies either underway or completed at UVA, and their implications for patients and for the ongoing pandemic, are summarized below.
A single-site trial based at UVA, the study examines the use of convalescent plasma — derived from blood donated by recovered COVID-19 patients — to treat patients hospitalized with the virus, but not yet in intensive care. In theory, the antibodies in the plasma will bind to virus cells, blocking them from harming healthy cells.
“Convalescent plasma therapy has been around for more than 100 years, and there has been a lot of interest in it since COVID-19 appeared,” said Dr. Jeff Sturek, who specializes in pulmonary and critical care medicine and is the principal investigator for the trial. “We wanted to bring this therapy to UVA, to contribute to the development of the field and to offer our patients as many options as possible.”
The trial was approved in April and patients were enrolled at UVA from May to August. Researchers are now in the process of analyzing results, which look promising.
UVA is part of a multisite Adaptive COVID-19 Treatment Trial, or ACTT, testing the antiviral drug remdesivir in adults hospitalized with COVID-19.
Results from the first part of the trial found that the drug sped recovery time in patients with advanced cases of COVID-19, prompting the U.S. Food and Drug Administration to issue an emergency use authorization for remdesivir. It was the first drug authorized to treat COVID-19.
The trial is now in its third phase; it began with comparing remdesivir to a placebo drug, and then progressed to pairing different drugs with remdesivir, to see which combination was most effective.
“The trial was designed to be iterative, to allow us to continue to adapt the study as we learn more about the drug,” Duska said. “That lets us continually improve treatment without having to go through a complete restart.”
Mesenchymal Stem Cells
Another multisite trial that includes UVA is investigating if infusion of the mesenchymal stromal cell remestemcel-L, a type of stem cell derived from bone marrow, can increase survival rates among COVID-19 patients experiencing acute respiratory distress syndrome.
The cells have been shown to migrate to the lungs when inflammation occurs and release anti-inflammatory factors that can reduce cytokines secreted by the immune systems. High levels of cytokine production have been associated with severe illness and death among COVID-19 patients.
“These adult bone marrow stem cells have been used to treat a variety of inflammatory diseases, which means they have already been through early safety trials and we could move more quickly into a larger trial,” said Sturek, also the principal investigator for this trial. “We hope that the cells can turn down inflammation in the lungs and help the lungs repair themselves, especially for critical ill patients on ventilators.”
The trial is halfway through its enrollment process, with a target of enrolling 300 patients. It has already passed initial safety checks with the National Institutes of Health’s Data Safety Monitoring Board.
In this multisite trial, researchers are working to determine if monoclonal antibodies made by the drug company Regeneron Pharmaceuticals can prevent COVID-19 infection among people who have been exposed by someone in their household, but have not yet developed the disease. The trial is testing the same antibody cocktail given to President Trump when he was hospitalized with COVID-19, though with a different use.
“In this case, the antibodies are intended to prevent people from getting sick if they have a household member with COVID,” Enfield said. “So far, UVA has done a good job with recruitment, which is particularly tricky in this case as you have to find people who have been exposed to COVID in their household, but who do not yet have COVID.”
UVA is recruiting 40 participants for the study, each of whom will receive four injections of either the antibodies or a placebo. Participants must have been exposed to COVID-19 by someone in their household within the previous 96 hours and continue to live with that person for a month.
“It’s been a rapid process, and a testament to the multidisciplinary team involved, from infectious disease clinicians and researchers to cell therapy, pulmonary critical care and several other departments,” Sturek said. “It’s been all-hands-on-deck.”