Auxora Vs. Placebo for the Treatment of Patients with Severe COVID-19 Pneumonia: A Randomized Clinical Trial

Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. Methods: : CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and encroachment of prohibited medications as standard of care, the trial was stopped early. Results: : The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO 2 /FiO 2 £200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days ( P =0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo ( P =0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively ( P =0.0165). Similar trends were noted in patients on high flow nasal cannula at baseline or those with a baseline imputed PaO 2 /FiO 2 ≤100. Serious adverse events occurred less frequently in patients treated with Auxora vs. placebo. Conclusions: : Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in combination with corticosteroids and other immunomodulatory agents are warranted. Trial registration: NCT04345614