Physicians are studying whether vadadustat, an investigational therapy, could protect the lungs of COVID-19 patients by triggering the body’s protective response to low oxygen levels in a randomized Phase II clinical trial at The University of Texas Health Science Center at Houston (UTHealth).
Vadadustat is designed to mimic the physiologic response to hypoxia (low oxygen). At higher altitudes, the body responds to lower oxygen availability with stabilization of hypoxia-inducible factor (HIF), which can lead to increased red blood cell production and improved oxygen delivery to tissues. As an investigational therapy, vadadustat is not approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority. Vadadustat, by Akebia Therapeutics, is in Phase III clinical trial development for anemia in chronic kidney disease patients.
Previously published preclinical studies led by Holger Eltzschig, MD, PhD, chair of the Department of Anesthesiology with McGovern Medical School at UTHealth, showed HIF stabilization can also protect lungs in mice with acute respiratory distress syndrome (ARDS), a disease that can develop from COVID-19 and one of the main causes of death from the virus.
Eltzschig and Bentley J. Bobrow, MD, chair of the Department of Emergency Medicine at McGovern Medical School, will lead a team of researchers to study whether vadadustat can help prevent and lessen the severity of ARDS and pneumonia in COVID-19 patients. Lung injury is among the most dangerous consequences of COVID-19 infection.
“Our research team found that without HIFs in the inner lining of lungs, mice had more lung inflammation and shorter survival time during ARDS. Using treatments that can cause the body to turn on HIF has been shown to decrease lung inflammation and fluid in the lungs, and improve survival in animal models,” said Eltzschig, the John P. and Kathrine G. McGovern Distinguished University Chair and the director of the UTHealth Center for Perioperative Medicine.
“Our previous published research has shown that this type of HIF PHD inhibitor also improves the efficiency of carbohydrate metabolism in injured lungs, which helps the lungs adapt to their injurious conditions and reduce inflammation in animal models,” Eltzschig said.
For the study in COVID-19 patients, the FDA granted the team at UTHealth an investigator-initiated Investigational New Drug (IND) Application, which is an authorization to give an investigational therapy to humans.
“Acute lung injury like ARDS is devastating and there are very few effective treatment options,” said Bobrow, the John P. and Katherine G. McGovern Distinguished Chair in emergency medicine. “Right now, we can support patients with COVID-related ARDS with supplemental oxygen and different forms of ventilation, but don’t yet have effective treatments to protect their lungs and help them get better. Our goal is to prevent patients with the virus from progressing to requiring a ventilator, and if they do require a ventilator, to decrease the time they are on that ventilator.”
The randomized trial will enroll up to 300 patients with COVID-19 who require supplemental oxygen to receive either oral vadadustat or placebo. The trial will start at Memorial Hermann Health System and expand to other sites across the U.S. if initial results are promising.
The study is funded by UTHealth’s Center for Clinical and Translational Sciences and Akebia Therapeutics, Inc.