Rigel Pharmaceuticals announced enrollment of the first patients in a multicenter, Phase 2 trial to evaluate the safety of fostamatinib, Rigel's oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of hospitalized COVID-19 patients. The study is sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), in collaboration with Inova? Health System. Fostamatinib, marketed in the U.S. as TAVALISSE? (fostamatinib disodium hexahydrate) tablets, is approved in the U.S. and Europe as a treatment for adult chronic immune thrombocytopenia (ITP).

"As mortality continues to rise, it is evident that new therapeutics selectively targeting immune response are desperately needed to treat patients infected with SARS-CoV-2," said Dr. Richard Childs, M.D., clinical director of the NHLBI. "This is a rigorously-designed clinical trial, which should provide insight into the potential safety and efficacy of fostamatinib in the treatment of severely ill patients suffering from COVID-19."

The clinical trial is being conducted at the NIH Clinical Center in Bethesda, Maryland and Inova Fairfax Hospital.

"We are very excited to be a part of this clinical trial with the NIH/NHLBI and Rigel. This study fits seamlessly within our portfolio of research options that we have within the Inova Health System to offer our COVID-19 population," said Dr. Steven Nathan M.D., medical director, Advanced Lung Disease & Lung Transplant Program, at Inova. "Research into novel compounds is a key component in finding therapeutic options for COVID-19 patients, and with the first patients enrolled, we are one step closer to understanding the potential of fostamatinib and SYK inhibition in this disease."

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 matched placebo (1:1) to approximately 60 evaluable patients who are a 5 to 7 on the 8-point ordinal scale (requiring supplemental oxygen via nasal canula or non-invasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation). Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to 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.

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 resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis. 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.

SYK is involved in the intracellular signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor (FcγR) and c-type lectin receptor (CLR) mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation. Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.