3D print of the influenza virus. Credit: National Institutes of Health.

The upcoming flu season is just around the corner, and an ongoing challenge for researchers has been how to best respond to cases of severe influenza in the event of an outbreak.

The Frederick National Laboratory for Cancer Research has helped the National Institute of Allergy and Infectious Diseases (NIAID) to coordinate a clinical trial to determine if immune plasma could be an effective treatment for cases of severe influenza. The randomized controlled study is the first of its kind to rigorously assess this type of therapy.

John Beigel, M.D., medical affairs scientist, Frederick National Lab, served as protocol chair for the Phase II clinical trial that included 29 academic medical centers across the country to assess the safety and efficacy of anti-influenza plasma. 

There were 98 participants in the study who were hospitalized with cases of severe influenza, randomly assigned to receive either standard care alone or anti-influenza plasma plus standard care, and monitored for 28 days. The research group published its findings in The Lancet Respiratory Medicine in June 2017.

Beigel said that the results showed some evidence of benefit to participants who received immune plasma, including fewer days spent in the hospital, faster time to when they had lower respiratory rates and didn’t require oxygen, and fewer days on mechanical ventilation. In addition, they were generally in a better clinical state (using a six-step scale) by the seventh day of treatment than those who just received standard care. 

“We believe that the multitude of findings all point in the direction that this is likely a true finding,” Beigel said. “It did allow us to develop and start a definitive Phase III study, and that study is ongoing right now.”

According to the Centers for Disease Control and Prevention, 4,605 people died from influenza in the United States in 2014. There has been a growing need for improved, cost-effective therapeutics for severe flu. There are a number of new drugs in development, but there have yet to be any therapeutics that have shown improved outcomes in hospitalized patients.

“This is a group with considerable morbidity and mortality,” explained Beigel. “Coupled with that is the fact that many new drugs come in at a very high cost point. With the ability to have novel influenza therapeutics available to a wide population for a public health intervention, including many countries that can’t afford these novel therapeutics, plasma treatment may be coming in at a much more reasonable cost point.”

Conducting this type of clinical trial on a large scale can present numerous challenges because it can be difficult to identify and enroll a hospitalized population with severe influenza. It also adds complexity in study management working with blood products. The plasma requires antibodies that have activity toward the circulating flu strains, which frequently change. This is the reason there are new vaccines each year. Plasma also needs to be matched at each clinical site with all of the different patient blood groups, adding an additional layer of complexity.

However, the encouraging findings from the Phase II trial helped researchers better understand treatment effects using plasma, which led to the much larger Phase III study currently underway. Beigel said that the study is just over 50 percent complete, with 82 subjects randomized out of 150.

The clinical trial is part of a much larger portfolio by NIAID to evaluate the approach of antibody administration for treatment of the flu. A complimentary study is also ongoing that is using concentrated antibodies and all other proteins removed (called immune globulin, or IVIG for short) to test its efficacy.

Beigel said that the Frederick National Lab study is expected to be completed by 2019, depending on the severity of the upcoming flu seasons.

“There have never been large randomized studies to assess immune plasma for the treatment of the flu,” he said. “All prior studies have been case series or cohort studies. There has been a lot of anecdotal data, but this is the first large study to really evaluate this approach.” 

By Max Cole, staff writer

Image: 3D print of the influenza virus. Credit: National Institutes of Health.