Abstract PO-002: RUXCOVID: A phase 3, randomized, placebo-controlled study evaluating the efficacy and safety of ruxolitinib in patients with COVID-19–associated cytokine storm

Abstract

Abstract Background: Severe COVID-19 can result in pneumonia, with many patients (pts) requiring hospitalization and oxygen support. Severe COVID-19 may also be complicated by acute respiratory distress syndrome, sepsis and septic shock, and/or multiorgan failure. Many of these pts have features consistent with cytokine release syndrome (CRS) and its associated hyperinflammation. Given their immunomodulatory effects, Janus kinase (JAK) inhibitors have been suggested as a potential therapeutic option in pts with severe COVID-19. Ruxolitinib—a potent JAK1/JAK2 inhibitor approved for treating myelofibrosis, polycythemia vera, and steroid-refractory acute graft-vs.-host disease (GvHD; US only)—has been associated with reduced levels of inflammatory cytokines in disorders where cytokine dysregulation plays a role, including GvHD and secondary hemophagocytic lymphohistiocytosis. Additionally, findings from a small, randomized, phase 2 study (N = 43; Cao Y et al., J Allergy Clin Immunol 2020) showed that treatment with ruxolitinib plus standard of care (SOC) reduced CRS-associated hyperinflammation in pts with severe COVID-19 vs placebo plus SOC, with significant improvement seen in chest computed tomography (CT) features. Although no statistically significant differences were observed, ruxolitinib-treated pts also had a numerically shorter median time to clinical improvement, a lower proportion requiring intensive care/mechanical ventilation, and reduced mortality, with ruxolitinib having a favorable safety profile. Methods: RUXCOVID (NCT04362137) is a global, randomized (2:1), double-blind, placebo-controlled, 29-day, phase 3 study evaluating the efficacy and safety of ruxolitinib plus SOC compared with placebo plus SOC in pts with COVID-19. Pts are eligible for the study if they are ≥ 12 years old, have confirmed COVID-19, are hospitalized, and meet ≥ 1 of the following: pulmonary infiltrates (by chest x-ray or CT scan), respiratory frequency ≥ 30 breaths/min, requirement of supplemental oxygen, oxygen saturation (SpO2) ≤ 94% on room air, or arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) < 300 mm Hg (1 mm Hg = 0.133 kPa). Pts with a need for intensive care or intubation are not eligible. Pts will be randomized to ruxolitinib 5 mg twice daily or placebo and treated for 14 days. Pts may be treated for an additional 14 days if no improvement occurs and the potential benefit outweighs the potential risk per investigator assessment. The primary endpoint is the proportion of pts who die, develop respiratory failure (require mechanical ventilation), or require intensive care by day 29. Secondary endpoints include improvement in clinical status, in-hospital outcomes, change in National Early Warning Score, change in SpO2:FiO2 ratio, mortality rate, change in inflammatory biomarkers, and safety. Target enrollment is 402 pts. Sponsored by Novartis Pharmaceuticals and Incyte. Citation Format: MeiLan K. Han, Rachel Ann Bender Ignacio, Amparo Lopez Bernus, Katrin Milger-Kneidinger, Amesika N. Nyaku, Ben Parker, Victoria Potter, Sinisa Savic, Valerie Campello-Iddison, Weihua Cao, Peter Langmuir, Barbara Knorr. RUXCOVID: A phase 3, randomized, placebo-controlled study evaluating the efficacy and safety of ruxolitinib in patients with COVID-19–associated cytokine storm [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-002.