Title : Efficacy of oral 20-hydroxyecdysone (BIO101) in adults with severe COVID-19 (COVA): A randomized, placebo-controlled, phase 2/3 trial
Abstract:
Background: SARS-CoV-2 infects human cells through interaction between its spike protein, and ACE2, a key element of the RAS. Thus SARS-CoV-2 may induce an imbalance of the RAS leading, among other symptoms, to severe pneumonia associated with COVID-19. We hypothesized that MAS-receptor activation by 20-hydroxyecdysone (20E) could modulate the protective arm of the RAS, leading to a reduced rate of respiratory failure and early death among hospitalized patients with COVID-19.
Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral 20E (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery.
Results: 238 patients were randomized between August 26, 2020, and March 8, 2022. At day 28, a reduction in the risk of early death or respiratory failure was observed: 43.8% (p=0.0426) (HR 0.44) in the ITT population; and HR 0.41 (p=0.037) in the PP population. On day 28, proportions of patients discharged after recovery were 80.1%, and 70.9% in the 20E and placebo groups respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p=0.0586). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group (22.7% vs. 31.7%) respectively.
Interpretation: 20E significantly reduced the risk of death or respiratory failure. This finding suggests that 20E is an important drug candidate to treat adults hospitalized with severe respiratory symptoms due to COVID-19.
