Researchers evaluating whether an investigational oral drug, vadadustat, can help prevent acute respiratory distress syndrome (ARDS) in COVID-19 patients were awarded $5.1 million in funding from the U.S. Department of Defense (DOD) to expand the Phase II clinical trial at The University of Texas Health Science Center at HoustonQ (UTHealth).
Vadadustat is an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, or HIF-PHI, designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower oxygen availability with stabilization of HIF, which can lead to improved oxygen delivery to tissues. Stabilization of HIF can help to dampen alveolar inflammation, a key problem that patients with COVID-19-associated lung disease are facing when they develop ARDS. The drug is investigational in the U.S. but has been approved for use in Japan.
It's wonderful that we have COVID-19 vaccinations available now, but they won't directly help patients who are already sick in the hospital or who will become sick in the future. In addition to vaccination, we direly need treatments to prevent ARDS, one of the deadliest complications of severe COVID-19. If we can arrest coronavirus infection at an earlier stage before the onset of lung complications that cause mortality, COVID-19 outcomes would be so much better."
Holger Eltzschig, MD, PhD, Chair of the Department of Anesthesiology with McGovern Medical School at UTHealth
Eltzschig is also director of the UTHealth Center for Perioperative Medicine and the John P. and Kathrine G. McGovern Distinguished University Chair.
The award was given through the DOD's Peer Reviewed Medical Research Program as a COVID Clinical Trial Award. Only 4.2% of all applications submitted were awarded funding.
"This study could be critical for people in active duty with the armed forces as well as veterans," Eltzschig said. "COVID-19 has had a particular impact on the Navy, where personnel on vessels such as aircraft carriers are in close environments and are unable to socially distance. If an innovative oral investigative therapy could prevent ARDS, that would be wonderful. Also, our country's veterans tend to be older, have comorbidities, and are particularly suffering from dire consequences of COVID-19, so it would be fantastic to be able to help them as well."
Vadadustat, being developed by Akebia Therapeutics, Inc., recently completed its global Phase III clinical trial development for the treatment of anemia due to chronic kidney disease in patients on dialysis and not on dialysis, and Akebia expects to submit a New Drug Application (NDA) for vadadustat to the FDA for these indications as early as possible in 2021.
Previously published preclinical studies led by Eltzschig, showed HIF stabilization can protect lungs in mice with ARDS. His basic and translation science team in anesthesia is collaborating with the clinical team of Ben Bobrow, MD, chair of Emergency Medicine at McGovern Medical School, to move the idea from bench to bedside to see if it can help COVID-19 patients.
"Dr. Bobrow and his clinical team of nurses and researchers helped us build up the trial quickly. I've never seen a clinical trial go from just an idea in March to enrolling patients in four months. It's really remarkable and we couldn't have done it without Akebia, UTHealth's Center for Clinical and Translational Sciences, and the collaboration between Bobrow's clinical group with my translational group," Eltzschig said.
"So many people and departments at UTHealth, Memorial Hermann, and Harris Health have come together to bring this cutting-edge trial together faster than ever before to try to help people suffering from COVID-19 acute lung injury. Dr Eltzschig and I are inspired by the potential for this novel trial to make a major impact on COVID-19 patients," said Bobrow, who is the John P. and Katherine G. McGovern Distinguished Chair in emergency medicine. Bobrow and Eltzschig are attending physicians at Memorial Hermann-Texas Medical Center.
The randomized trial began enrolling patients at Memorial Hermann-Texas Medical Center in July. The DOD funding helped the trial expand to Memorial Hermann-Southwest Hospital, Memorial Hermann Greater Heights Hospital, and Memorial Hermann Memorial City Medical Center, as well as Harris Health's Lyndon B. Johnson Hospital. Currently, 75 patients have enrolled.
"It's unclear how long COVID-19 will be prevalent so it is critical to expand the single center trial to other sites," Eltzschig said.
The trial was initially funded by Akebia Therapeutics, Inc. and a donor grant to UTHealth's Center for Clinical and Translational Sciences.