Introduction: This trial evaluated the benefit of BIO101 (20-hydroxyecdysone), a MAS receptor activator, in severe Covid-19

Aims and objectives: Assess the efficacy and safety of BIO101 in hospitalized COVID-19 patients.

Methods: Randomized, placebo controlled Phase2/3 trial. Hospitalized adults aged ≥45 years with respiratory decompensation due to Covid-19 were randomized 1:1 to placebo (PLB) or BIO101 (350mg bid) for up to 28 days. Primary endpoint: proportion of patients with death or respiratory failure at day 28. Planned sample: 310 patients.

Results: In ITT group: 233 patients (63.5% male, age 62.8 years) and 180 in the Per Protocol (PP) analysis. Groups were balanced but PLB used more immunosuppressants (8.4% vs 3.2%). The primary analysis showed a trend towards statistical significance favoring BIO101 (BIO101: 13.5%, PLB: 24.3%), adjusted difference 11.8% (p=0.078), a relative risk (RR) reduction of respiratory failure or death of 45.4% at day 28. Using Kaplan-Meier (KM) analysis, difference in proportion of patients with death or respiratory failure between BIO101 and PLB was nominally statistically significant at day 28 (10.9%, p=0.037), a 44.0% RR reduction. In post-hoc KM analyses hazard ratio was 0.586 (log-rank p=0.160) for the comparison of curves at Day 90, a 9.3% reduction in mortality (RR reduction, 42.9%, p=0.076) in the ITT population and an 11.7% reduction (RR reduction, 69.6%, p= 0.016) in the PP population. No clear differences occurred except an increase in respiratory-related adverse events on PLB.

Conclusion: BIO101 showed a strong trend to reduce the risk of death or respiratory failure, strongly supported by post-hoc analyses.