Cova Results From a Double-Blind, Placebo-Controlled Phase 2/3 Study to Assess Efficacy and Safety of BIO101 in Hospitalized Severe COVID-19 Patients

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Conference Proceeding

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Publication Title

American Journal of Respiratory and Critical Care Medicine


RATIONALE This trial assessed whether BIO101 (20-hydroxyecdysone), a MAS receptor activator targeting the Renin-Angiotensin-System, may provide benefit in patients with severe Covid-19.METHODS Randomized, placebo-controlled phase 2/3 trial. Adults ≥45 years with respiratory decompensation by SARS-CoV-2 needing hospitalization (but not mechanical ventilation) were randomized 1:1 to placebo or BIO101 (350 mg bid) for up to 28 days, until hospital discharge or respiratory failure. Primary endpoint: the proportion of patients who died or required high-flow oxygen, mechanical ventilation or ECMO was analysed using Cochran-Mantel-Haenszel (CMH) test. Planned sample size: 310 subjects to detect a relative decrease of 37.5% between BIO101 (25%meeting endpoint) and placebo (40% meeting endpoint). Key secondary endpoint: proportion of patients recovered and discharged. Unless otherwise specified, results are from ITT population. RESULTS The trial ended early for stalled recruitment. ITT population: 233 patients (63.5% male, mean age 62.8 years). Per Protocol (PP) population: 180 patients. Groups were balanced except for placebo group taking more immunosuppressants (8.4% vs 3.2%). Primary (CMH) test at day 28showed a statistically significant difference favoring BIO101 (BIO101: 15.8%, placebo: 26.0%),adjusted difference 11.4% (p=0.042), a relative risk (RR) reduction of early death or respiratory failure of 44% (greater than expected). This difference was supported by post-hoc KM analyses that show a significant 44% relative reduction in the risk of early death or respiratory failure at day 28(p=0.037, ITT). A difference was also seen for time to respiratory failure or early death showing a nominally statistically significant difference over 28 days (Hazard ratio=0.49, stratified log rank p=0.022). Proportion of recovered patients showed a strong trend towards benefit of BIO101(adjusted difference 11.0%, p= 0.059). In a post hoc KM at day 90, the relative risk of death was reduced by 43% in the ITT population (p=0.076), and by 70% in PP population (p=0.016). Safety and tolerability of BIO101 was very good: less patients treated with BIO101 experienced adverse events (AEs) compared to placebo (57.0% vs 64.4%), due to higher incidence of respiratory events in the placebo group. CONCLUSIONS BIO101 was effective in reducing the risk of death or respiratory failure in the first 28 days in primary analysis of a hospitalized Covid-19 population by11.4% (RR reduction: 44%), strongly supported by secondary and post-hoc analyses. Risk of death at day 90 and proportion of discharged patients showed strong trends towards benefit of BIO101.





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American Thoracic Society International Conference, May 19-24, 2023, Washington, D.C.