Safety and Efficacy of Dapansutrile for Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome

Study Summary

The purpose of this study is to assess the safety and efficacy of orally administered NLRP3 inhibitor, dapansutrile, for the treatment of moderate COVID-19 symptoms and early cytokine release syndrome (CRS) in patients with confirmed SARS-CoV-2 infection and moderate symptoms. Coronavirus disease 2019 (COVID-19) is caused by infection from a new strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is characterized by fever, cough and shortness of breath, which in certain patients can lead to systemic organ failure and mortality. The data show that SARS-CoV-2 activates the innate immune signaling sensor NLRP3. Activation of NLRP3 initiates the cytokine release syndrome (CRS), which includes the production of primary cytokine, IL-1, triggering an intense inflammatory response that is prevalent in symptomatic COVID-19 patients. When CRS advances further to a fulminant 'cytokine storm', the data show that respiratory distress syndrome and multiple-organ failure take place. A specific inhibitor of NLRP3, dapansutrile may reduce or prevent the hyperinflammation associated with CRS by inhibiting the production of IL-1β early to arrest the progression to a severe 'cytokine storm.' The end result would be a reduction in the need for COVID-19 patients to receive intensive medical treatment, allowing for fewer hospitalizations, administration of mechanical ventilation and deaths.

Primary Outcome

Clinical deterioration is defined as having any COVID-19-related hospitalization after enrollment or both (1) worsening or persistence of shortness of breath and (2) oxygen saturation less than 92% on room air at sea level or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.

Interventions

• DRUG placebo capsules
• DRUG dapansutrile capsules