Inova Partners with NIH’s NHLBI on New Clinical Trial for Hospitalized COVID-19 Patients
Study enrollment complete with topline data expected in April 2021
Falls Church, VA – Inova Lung Services is part of a multicenter Phase 2 investigator-sponsored trial (IST) to evaluate the safety of fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of hospitalized COVID-19 patients. The study is in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). Fostamatinib is marketed in the U.S. under the brand name TAVALISSE® (fostamatinib disodium hexahydrate) tablets. The product is approved in the U.S. and Europe as a treatment for adult chronic immune thrombocytopenia (ITP).
“With the ongoing pandemic continuing to cause tens of thousands of new daily cases of COVID across the U.S., there is a critical need to not only stop the spread of the virus, but to also develop new and effective therapies to treat the infected population, including those with severe and life-threatening disease,” said Richard Childs, M.D., Clinical Director of the NHLBI. “As we work with the broader community to identify safe and effective therapeutic options for COVID-19 patients, we are hopeful that the investigation of fostamatinib will potentially aid in the fight against this pandemic.”
The IST is being conducted at the NIH Clinical Center in Bethesda, Maryland, the nation’s largest hospital devoted entirely to clinical research, Inova Fairfax, and potentially other Inova hospitals.
“We are very excited to be participating in this study. This collaborative effort resulted from our close pre-existing collaboration with NIH, which has been further solidified as we all redirect our research efforts to tackle COVID-19. This study will fit seamlessly within our portfolio of research options that we have within the Inova Health System to offer our COVID-19 population. Aside from well-established preventative strategies, research into novel compounds is the only way we will impact the potentially devastating impact of this virus. Through our research we are taking the fight to the virus,” said Steven Nathan, M.D., Medical Director Inova Advanced Lung Disease and Lung Transplant Program.
COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS). Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock along with endothelial dysfunction and subsequently micro and macrovascular thrombosis.1 Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a hyperinflammatory immune response associated with increased risk of thrombosis.2
SYK inhibition may improve outcomes in patients with COVID-19 by reducing inflammation that can cause organ dysfunction in patients with COVID-19 who become critically ill.
This is a randomized, double-blind, placebo-controlled trial to evaluate the safety of fostamatinib for the treatment of hospitalized COVID-19 patients. The study will randomly assign fostamatinib or a placebo to approximately 60 patients. Treatment will be administered orally twice daily for 14 days. There will be a follow-up period Day 60. The primary objective of this study is to evaluate the safety of fostamatinib compared to placebo for the treatment of hospitalized COVID-19 patients. The secondary objective will be to assess the early efficacy and clinically relevant measures of disease progression.
Recently, researchers at The Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard led a recent screen focused on drug repurposing to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. MUC1 is a biomarker used to predict the development of acute lung injury (ALI) and ARDS and correlates with poor clinical outcomes. Of the 3,713 compounds that were screened, fostamatinib was the only compound identified which both decreased expression of MUC1 and is FDA approved.3 Additionally, a recent study led by the Amsterdam University Medical Center at the University of Amsterdam, found that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyperinflammatory response by human macrophages, a response that can be counteracted by SYK inhibition with fostamatinib. This study also found that anti-Spike IgG can break down pulmonary endothelial barriers and induce microvascular thrombosis.4 Fostamatinib is currently in a Phase 2 investigator-sponsored trial being conducted by Imperial College London to evaluate the efficacy of fostamatinib for the treatment of COVID-19 pneumonia.
1. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 2020
2. Becker RC. COVID-19 Update: COVID-19 associated coagulopathy. Journal of Thrombosis and Thrombolysis May 15, 2020. DOI: https://doi.org/10.1007/s11239-020-02134-3
3. Alimova M. et al. A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic. bioRxiv June 30, 2020. DOI: https://doi.org/10.1101/2020.06.30.180380
4. Hoepel W. et al. Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses. bioRxiv July 13, 2020. DOI: https://doi.org/10.1101/2020.07.13.190140
About Inova
Inova is Northern Virginia’s leading nonprofit healthcare provider, recognized in 2019 and 2020 by U.S. News & World Report, which named Inova Fairfax Hospital the #1 hospital in the Washington, DC region. All five Inova hospitals were awarded ‘A’ grades for the spring 2020 Leapfrog Hospital Safety Grades, recognizing Inova’s achievements in protecting patients from harm and providing safer healthcare. Each of Inova’s five hospitals holds a 5-star rating from the Centers for Medicare & Medicaid Services (CMS), distinguishing Inova as the highest-rated large health system in the U.S., and the only system to have all hospitals receive five stars. Inova Fairfax Medical Campus was named to the Fortune/IBM Watson Health 100 Top Hospitals list, ranking in the top 10 nationwide among Major Teaching Hospitals. Our mission is to provide world-class healthcare – every time, every touch – to each person in every community we have the privilege to serve. Inova’s 18,000 team members serve more than 2 million individuals annually through an integrated network of hospitals, primary and specialty care practices, emergency and urgent care centers, outpatient services and destination institutes. Inova is home to Northern Virginia’s only Level 1 Trauma Center and Level 4 Neonatal Intensive Care Unit. Its hospitals have a total of 1,800 licensed beds. More information and statistics about Inova can be found at www.inova.org.