May 6, 2020
Virginia Commonwealth University has become one of the first sites in the world to begin clinical trials to study the safety and efficacy of the drug canakinumab on patients experiencing a type of severe immune overreaction called cytokine release syndrome, which occurs in some patients with pneumonia due to COVID-19.
Canakinumab works to neutralize a protein, Interleukin-1β, in the body in order to suppress deregulated inflammation. It is FDA approved to treat a series of rare auto-inflammatory diseases and a type of juvenile arthritis, Systemic Juvenile Idiopathic Arthritis.
“Interleukin-1β is an important cytokine that mediates fever and causes a cascade of inflammation in the body and is considered to be one of the key mediators in inflammatory response,” said Antonio Abbate, M.D., Ph.D., the study’s principal investigator and a cardiologist at VCU Health.
The study activated on April 29, and Abbate’s team has begun screening potential participants for enrollment. The drug’s manufacturer and trial sponsor, Novartis, hopes to bring more centers worldwide online in the coming weeks to expand patient enrollment to 450 total.
“Because of our familiarity with the drug and because we were intimately involved with VCU's COVID-19 response, all the stars aligned and we were able to get this trial up and running really quickly,” said Benjamin Van Tassell, Pharm.D., a professor in VCU’s School of Pharmacy and a co-investigator on the study.
With this phase 3 trial, researchers seek to confirm the safety and efficacy of canakinumab with a multicenter, randomized, placebo-controlled study. Researchers will enroll volunteer COVID-19 patients who are experiencing cytokine release syndrome and who require oxygen but do not need a ventilator.
Abbate, Van Tassell and VCU were involved in a previous study of canakinumab where it was shown to reduce recurrent cardiovascular events, independent of lipid lowering.
“When you have heart disease, the [disease] triggers inflammation, and the inflammation can, in turn, accelerate the disease,” Van Tassell said. “So we've been spending the better part of a decade trying to figure out how we could shut down that inflammation in a safe way. And Interleukin-1β, this inflammatory protein, seems to be the spark that triggers everything else. So if you can shut down that spark, you have a good chance of shutting down that inflammatory process.”
As VCU and hospitals worldwide work to combat the coronavirus from a number of angles, Abbate and Van Tassell are also interested in impeding the symptoms’ progression from moderate to severe to fatal. And the inflammation, Van Tassell said, may be what’s actually fatal.
“It can kind of snowball on itself,” he said. “A little bit of inflammation can trigger more inflammation, which triggers more and more. And that seems to be the most dangerous part of a COVID-19 infection: when you enter into this hyper-inflammatory state.”
There's preliminary evidence that focusing on drugs that combat that is a good strategy for saving lives. And Van Tassell says Interleukin-1β-blocking strategies may have the most promising safety data so far.
This study joins other drug treatment trials already active at VCU, including two trials with an antiviral drug developed for Ebola, remdesivir, and another with a drug developed to treat rheumatoid arthritis, sarilumab. In an April 29 release by Gilead Sciences, results of a clinical trial for patients with severe COVID-19 symptoms showed that remdesivir has promise as a treatment of COVID-19. These preliminary results were from 180 sites, including VCU Health. The FDA issued an emergency use authorization for remdesivir May 1.
“As providers around the world seek to find the best course of treatment for COVID-19 patients, our researchers across VCU and VCU Health are doing the hard work of ensuring the safety and efficacy of potential future treatment options,” said Peter Buckley, M.D., dean of the VCU School of Medicine and interim senior vice president for VCU Health Sciences and CEO of VCU Health. “We are grateful to our teams for making investigational drug therapies a seamless part of our care and generating the data necessary to potentially make a variety of treatment options available to future COVID-19 patients nationally and globally.”
Abbate notes that there is a lot still unknown about COVID-19 and its symptoms. Clinical trials are trying to adapt to the data and information in real time. “It’s clear that at different stages of the disease, you’re trying to prevent different things,” he said.
Abbate is also the medical director of the Clinical Research Unit at VCU Health and an associate director at the C. Kenneth and Dianne Wright Center for Clinical and Translational Research, which oversees clinical trials at VCU with the help of a National Institutes of Health award. The Clinical Research Unit is a unique, dedicated space at VCU Health used for clinical trials, and its committed staff of nurses has been heavily involved in COVID-19 trials.
“With all of the moving pieces in the COVID-19 pandemic, it has really helped to be at a place like VCU that has the experience, the infrastructure, the personnel and the will to do this kind of trial,” Van Tassell said. “The best access to promising treatments has been through clinical trials, and, in that sense, VCU has been fortunate to have an established clinical trials program that can open its doors to developing and emerging treatments.”
A previous version of this story included the term "immunosuppressant" to describe the drug canakinumab. Canakinumab suppresses a severe immune overreaction called cytokine release syndrome; it is not an immunosuppressant.
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