TY - JOUR
T1 - Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA)
T2 - a randomized, placebo-controlled, phase 2/3 trial
AU - Lobo, Suzana Margareth
AU - Plantefève, Gaétan
AU - Nair, Girish
AU - Joaquim Cavalcante, Adilson
AU - Franzin de Moraes, Nara
AU - Nunes, Estevao
AU - Barnum, Otis
AU - Berdun Stadnik, Claudio Marcel
AU - Lima, Maria Patelli
AU - Lins, Muriel
AU - Hajjar, Ludhmila Abrahao
AU - Lipinski, Christopher
AU - Islam, Shaheen
AU - Ramos, Fabiano
AU - Simon, Tiago
AU - Martinot, Jean Benoît
AU - Guimard, Thomas
AU - Desclaux, Arnaud
AU - Lioger, Bertrand
AU - Neuenschwander, Fernando Carvalho
AU - DeSouza Paolino, Bruno
AU - Amin, Alpesh
AU - Acosta, Samuel Amil
AU - Dilling, Daniel Forde
AU - Cartagena, Edgardo
AU - Snyder, Brian
AU - Devaud, Edouard
AU - Barreto Berselli Marinho, Ana Karolina
AU - Tanni, Suzana
AU - Milhomem Beato, Patricia Medeiros
AU - De Wit, Stephan
AU - Selvan, Vani
AU - Gray, Jeffrey
AU - Fernandez, Ricardo
AU - Pourcher, Valérie
AU - Maddox, Lee
AU - Kay, Richard
AU - Azbekyan, Anait
AU - Chabane, Mounia
AU - Tourette, Cendrine
AU - Esmeraldino, Luis Everton
AU - Dilda, Pierre J.
AU - Lafont, René
AU - Mariani, Jean
AU - Camelo, Serge
AU - Rabut, Sandrine
AU - Agus, Samuel
AU - Veillet, Stanislas
AU - Dioh, Waly
AU - van Maanen, Rob
AU - Morelot-Panzini, Capucine
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2024/2
Y1 - 2024/2
N2 - Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (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 (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [−0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.
AB - Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (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 (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [−0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.
KW - 20-Hydroxyecdysone
KW - COVID-19
KW - MasR
KW - Renin-angiotensin-system (RAS)
KW - Respiratory failure
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85185831544&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85185831544&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2023.102383
DO - 10.1016/j.eclinm.2023.102383
M3 - Article
AN - SCOPUS:85185831544
SN - 2589-5370
VL - 68
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102383
ER -