Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial.

Autor:	Lobo SM; Intensive Care Division. Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil., Plantefève G; Intensive Care Unit, Clinical Research Center and CRICS-Triggersep Network, Centre Hospitalier Victor Dupouy, 69 rue du lieutenant-colonel Prudhon, 95100, Argenteuil, France., Nair G; William Beaumont Hospital, 3601 W. 13 Mile Road, Royal Oak, MI, 48073, USA., Joaquim Cavalcante A; CEMEC - Centro Multidisciplinar de Estudos Clínicos, São Bernardo do Campo, São Paulo, Brazil., Franzin de Moraes N; Hospital Municipal de Barueri Dr. Francisco Moran, Barueri, São Paulo, Brazil., Nunes E; Instituto Nacional de Infectologia Evandro Chagas/ Fiocruz, Rio de Janeiro, Brazil., Barnum O; Barnum Medical Research, Inc, 1029 Keyser Ave, Suite H, Natchitoches, LA, 71457, USA., Berdun Stadnik CM; Santa Casa de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil., Lima MP; Hospital e Maternidade Celso Pierro - PUCCAMP, Campinas, São Paulo, Brazil., Lins M; AZ Sint-Maarten Department: Pneumology General Hospital Sint-Maarten, Liersesteenweg 435, 2800, Mechelen, Belgium., Hajjar LA; Instituto do Coração - INCOR, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo. HC-FMUSP, São Paulo, Brazil., Lipinski C; Abrazo Health, 2000 West Bethany Home Road Phoenix, AZ, 85015, USA., Islam S; Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA., Ramos F; Hospital São Lucas da Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil., Simon T; Instituto Méderi de Pesquisa e Saúde, Passo Fundo, Rio Grande do Sul, Brazil., Martinot JB; CHU-CLU Clinique et maternité Sainte Elisabeth CSME Namur, Department of Pneumology Place Louise Godin 15, Namur, 5000, Belgium., Guimard T; Centre Hospitalier Départemental de Vendée, Les Oudairies 85925 La Roche-sur-Yon cedex 9, France., Desclaux A; Le Tripode, Groupe hospitalier Pellegrin, Place Amélie Raba-Léon 33000 Bordeaux CHU Bordeaux, France., Lioger B; Service de médecine Interne et Polyvalente, Centre Hospitalier de Blois, Mail Pierre Charlot 41016 Blois CEDEX, France., Neuenschwander FC; Hospital Vera Cruz, Belo Horizonte, Minas Gerais, Brazil., DeSouza Paolino B; Hospital São Lucas SA, Rio de Janeiro, Brazil., Amin A; University of California, Irvine 333 City Blvd West, Suite 500 Orange, CA, 92868, USA., Acosta SA; Manati Medical Center Calle Hernandez Carrion, No. 668 Urb. Atenas Manati, PR, 00674, USA., Dilling DF; Loyola University Medical Center, 2160 S. 1st Ave blg 115 suite 253, Maywood, IL 60153, USA., Cartagena E; San Juan Bautista School of Medicine Clinical Research Unit/ Hospital Menonita Caguas, PR, 00725, USA., Snyder B; Catholic Health System, 2605 Harlem Road, Cheektowaga, NY, 14225, USA., Devaud E; Centre hospitalier René Dubos, Bâtiment A, 6 avenue de l'Ile de France, Cergy Pontoise, 95300, France., Barreto Berselli Marinho AK; Conjunto Hospitalar do Mandaqui, São Paulo, Brazil., Tanni S; UPECLIN - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP, Botucatu, São Paulo, Brazil., Milhomem Beato PM; Fundação Doutor Amaral Carvalho - Hospital Amaral, Jau, São Paulo, Brazil., De Wit S; CHU Saint-Pierre, 105, rue aux Laines, Brussels, 1000, Belgium., Selvan V; Texas Tech University Health Sciences Center, Department of Family and Community Medicine, 701 W 5th Street, Odessa, TX, 79763, USA., Gray J; United Health Services Hospitals, 33-57 Harrison Street, Johnson City, NY, 13790, USA., Fernandez R; FDI Clinical Research - San Juan City Hospital, 998 Muñoz Rivera Ave, San Juan, PR, 00927, USA., Pourcher V; Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié Salpêtrière-Charles Foix, 47-83 Boulevard de l'Hôpital, Paris Cedex 13, 75651, France., Maddox L; WellSpan York Hospital, 101 Shouth George Street, York, 17403, USA., Kay R; RK Statistics Ltd, Brook House, Mesne Lane, Bakewell, DE45 1AL, UK., Azbekyan A; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Chabane M; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Tourette C; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Esmeraldino LE; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Dilda PJ; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Lafont R; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France.; Sorbonne Université & CNRS - Institut de Biologie Paris Seine (BIOSIPE), 75005, Paris, France., Mariani J; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France.; Sorbonne Université & CNRS - Institut de Biologie Paris Seine, UMR 8256, 75005 Paris, France., Camelo S; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Rabut S; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Agus S; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France.; Actual address: Altus Care powered by Oberon Sciences, Israel., Veillet S; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Dioh W; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., van Maanen R; Biophytis - Sorbonne Université, BC9, 4 place Jussieu, 75005, Paris, France., Morelot-Panzini C; Service de Pneumologie, Groupe Hospitalier Pitié Salpêtrière, Sorbonne Université 47-83 Boulevard de l'Hôpital, Paris Cedex 13, 75651, France.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2024 Jan 03; Vol. 68, pp. 102383. Date of Electronic Publication: 2024 Jan 03 (Print Publication: 2024).
DOI:	10.1016/j.eclinm.2023.102383
Abstrakt:	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. Competing Interests: Biophytis declares that potential commercial interests had no impact on the scientific conduct of the study nor on the analysis/interpretation of data. Cendrine Tourette, Luis Esmeraldino, Pierre Jean Dilda, René Lafont, Serge Camelo, Sandrine Rabut, Waly Dioh, Rob van Maanen and Stanislas veillet are Biophytis company employees, Anait Azbekyan Samuel Agus and Mounia Chabane are former Biophytis company employees. Jean Mariani is emeritus professor at Sorbonne University and consultant for Biophytis, Richard Kay is a consultant for Biophytis. Alpesh Amin, MD declares that as principal investigator or co-investigator of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion, BioPhysitis its institution received payments and that he personnally received consultant fees from BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Ferring, Seres, Spero, Eli Lilly, Gilead, Millenium, HeartRite, Aseptiscope, and Sprightly; but that these relationships were unrelated to the current work. Shaheen Islam, MD declares that he received grants or was in contract as a principal or sub investigator from the following companies:–Pliant therapeutics: INTEGRIS-ARDS, drug (PLN74809) Covid -trial 2021 (PI).—CytoDyn, Inc.: CD12-COVID 19 Drug: Leronlimab COVID trial 2020 (PI). -Pluristem Ltd.: PLX-COV-01. Drug PLX-PAD, COVID Trial 2020 (Sub-I).—Edesa Biotech Inc.: EB05-04-2020. Drug: EB05 COVID Trial 2020 (Sub-I). Fabiano Ramos, MD declares that its institution: Hospital São Lucas da Pontíficia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, Brazil received financial resources to conduct the study from Biophytis. Brian Snyder, MD declares that he receives research funding from Biophytis as part of the present clinical trial. Moreover, he declares that he received grants or has contracts with Behring, and Rheonix as part of COVID research studies. None of the other investigators declare any relationship related to the current work. (© 2023 The Author(s).)
Databáze:	MEDLINE
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