August 14, 2020
The University of Kansas Medical Center announced today a trial exploring a drug intended to fight the cytokine storm common in COVID-19. A unique partnership between a researcher usually focused on cancer and a researcher usually focused on cystic fibrosis has resulted in an investigator-initiated clinical trial that joins the forces of KU Medical Center’s Department of Internal Medicine with those of The University of Kansas Cancer Center.
When 2020 began, Gregory Gan, MD, PhD, assistant professor of radiation oncology at KU Cancer Center, was all set to dive into new research on treatment resistance and metastasis in head and neck cancer. A few months and a global pandemic later, he’s partnered with pulmonologist Deepika Polineni, MD, MPH, associate professor in the KU School of Medicine, and they have launched a trial together exploring a drug to fight COVID-19.
They are enrolling participants now in this trial of a new investigational drug (ATI-450), developed by Aclaris Therapeutics, Inc., that Gan had wanted to study for its potential to slow metastasis in cancer. Now, he and Polineni are studying whether it can be used, in conjunction with standard-of-care therapy, to halt respiratory failure in patients hospitalized with COVID-19. If successful, this drug could potentially keep those patients from needing mechanical ventilation.
This new drug inhibits a protein Gan has been studying, MAP kinase-activated protein kinase-2 (MK2), for its potential role in blocking the effectiveness of treatments for head and neck cancers.
MK2 helps the body produce inflammatory cytokines, types of proteins released both by the body’s immune system and tissue. MK2 is also important in a process known as epithelial-to-mesenchymal transition (EMT), in which epithelial cells transform into a type of stem-like cell that helps organs develop and repairs damaged tissue. Both inflammation and EMT are necessary processes in healthy tissue. However, in cancer and perhaps in COVID-19, both processes become overactive.
Gan reached out to Polineni to partner as co-investigator. Together, the two researchers reached out to Aclaris about supporting a clinical trial to evaluate the potential of ATI-450 to treat people hospitalized with COVID-19, in conjunction with standard-of-care treatment.
“I guess it’s true what they say about lemons and lemonade,” said Gan. “I’m lucky in that the pathway I'm already studying actually may have a role for managing COVID-19.”
Polineni agreed. “The same cytokines this drug targets are also important to the inflammatory processes of lung disease I study in CF,” she said. “In the setting of infection, even with a virus like SARS-CoV-2 [the virus that causes COVID-19], some inflammation is required to aid in clearing infection, but a hyper-inflammatory response can lead to accelerated lung injury and worsened outcomes.”
Aclaris is supporting the trial and also providing the drug. KU Medical Center aims to enroll 36 patients age 18 or older who are hospitalized with COVID-19 and have respiratory symptoms. The participants will be consenting patients being treated at The University of Kansas Health System.
Half the patients will be randomized to receive the drug, and half will be randomized to receive a placebo. All patients will receive standard-of-care treatment during the trial, in addition to the drug or placebo. The researchers are primarily interested in the proportion of patients who are not suffering from respiratory failure at the end of 14 days.
The researchers also plan to use what they learn from the trial to inform their other, separate research projects on cancer and CF.
“As physicians, we always want to advance the public good, and as scientists, we want to remain productive. All the lessons we're going to learn from studying COVID-19 will hopefully help us design smarter studies in our respective areas and tell us a little bit more about the drug that we're studying,” said Gan. “And that is, I think, the best I could have hoped for in the middle of a pandemic crisis.”