Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial*. Issue 1 (14th November 2022)

• Record Type: Journal Article
• Authors: Waters, Michael; McKinnell, James A.; Kalil, Andre C.; Martin, Greg S.; Buchman, Timothy G.; Theess, Wiebke; Yang, Xiaoying; Lekkerkerker, Annemarie N.; Staton, Tracy; Rosenberger, Carrie M.; Pappu, Rajita; Wang, Yehong; Zhang, Wenhui; Brooks, Logan; Cheung, Dorothy; Galanter, Joshua; Chen, Hubert; Mohan, Divya; Peck, Melicent C.
• Other Names: Meena Nikhil author non-byline.; Waters Michael author non-byline.; Overcash Jeffrey author non-byline.; Mealey Forest author non-byline.; McKinnell James author non-byline.; Douglas Ivor author non-byline.; Buck Theresa author non-byline.; Mendez-Mulet Luis author non-byline.; Boyce Paul author non-byline.; Saberi Asif author non-byline.; Comellas Alejandro author non-byline.; Jaffrani Naseem author non-byline.; Jeanfreau Robert author non-byline.; Widmer Kyle author non-byline.; Ramesh Mayur author non-byline.; Perin Patrick author non-byline.; Neidhart Jeffrey author non-byline.; Beegle Scott author non-byline.; Menon Vidya author non-byline.; Wiznia Andrew author non-byline.; Hahn Barry author non-byline.; Borger Judith author non-byline.; Jauregui-Peredo Luis author non-byline.; Wells Jason author non-byline.; Gareca Marcelo author non-byline.; Criner Gerard author non-byline.; Jain Raksha author non-byline.; Jain Raksha author non-byline.; Sanyal Arun author non-byline.; Malhotra Uma author non-byline.; Malhotra Vinay author non-byline.; Nunes Estevão author non-byline.; Luz Kleber author non-byline.; Stadnik Claudio Marcel Berdun author non-byline.; Lima Maria author non-byline.; Lobo Suzana author non-byline.; Fiss Elie author non-byline.; Hajjar Ludhmila Abrahão author non-byline.; José Morales Reyes Juan author non-byline.; Mercado Longoria Roberto author non-byline.; Sifuentes Osornio José author non-byline.; Ramírez Venegas Alejandra author non-byline.; Navarro Álvarez Samuel author non-byline.; Molina María author non-byline.; Calbo Sebastián Esther author non-byline.; Míguez Rey Enrique author non-byline.; Oteo José author non-byline.; Olalla Julián author non-byline.; Gallego Juan Pablo Horcajada author non-byline.; Mediano Olga author non-byline.; Núñez-Cortes Jesús Millán author non-byline.; Marcos Martín Miguel author non-byline.; Dueñas Gutierrez Carlos author non-byline.; Peck Melicent author non-byline.; Mohan Divya author non-byline.; Chen Hubert author non-byline.; Theess Wiebke author non-byline.; Gall Jonathan author non-byline.; Galanter Joshua author non-byline.; Dash Ajit author non-byline.; Wong Tiffany author non-byline.; Yang Xiaoying author non-byline.; Wang Lena author non-byline.; Buchanan Jenny author non-byline.; Dokonal Kristina author non-byline.; Jurincic Valentine author non-byline.; Gray Hilary author non-byline.; Ma Lixian author non-byline.; Marchenko Irina author non-byline.; Spoonemore Holly author non-byline.; Tzovolos Ageliki author non-byline.; Gasser-Stracca Marina author non-byline.; Valentine Kit author non-byline.; Defreese Jessica author non-byline.; Flanagan Mike author non-byline.; Hurst Steve author non-byline.; Park Joo author non-byline.; Nelson Tasi author non-byline.; Horn Priscilla author non-byline.; Costante-Hamm Stella author non-byline.; McKinney Aubrey author non-byline.; Rosseig Julie author non-byline.; Roth Sarah author non-byline.; Whitmore Jennifer author non-byline.; Tran Ha author non-byline.; Abogado Catherine author non-byline.; Ahmed Zara author non-byline.; Hilton Jon author non-byline.; Kum Eric author non-byline.; Pon Jennifer author non-byline.; Sana Daniel author non-byline.; Ferdousy Elma Zannatul author non-byline.; Alexander Elaine author non-byline.; Staton Tracy author non-byline.; Lekkerkerker Annemarie author non-byline.; Sharp Andrea author non-byline.; Miley Natasha author non-byline.; Dolton Michael author non-byline.; Wang Yehong author non-byline.; Zhang Wenhui author non-byline.; Brooks Logan author non-byline.; Sperinde Gizette author non-byline.; Arjomandi Audrey author non-byline.; Kalo Matt author non-byline.; Ciullo Elisa author non-byline.;
• Is Part Of: Critical care medicine. Volume 51:Issue 1(2023)
• Page Start: 103
• Page End: 116
• Publication Date: 2022-11-14
• Subjects: acute respiratory distress syndrome -- biomarkers -- COVID-19 -- interleukin-22 -- interleukin-33; Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000005716
• Languages: English
• ISSNs: 0090-3493

Abstract

Abstract : OBJECTIVES: Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS. This study aimed to evaluate safety and efficacy of astegolimab, a human immunoglobulin G2 monoclonal antibody that selectively inhibits the IL-33 receptor, ST2, or efmarodocokin alfa, a human IL-22 fusion protein that activates IL-22 signaling, for treatment of severe COVID-19 pneumonia. DESIGN: Phase 2, double-blind, placebo-controlled study (COVID-astegolimab-IL). SETTING: Hospitals. PATIENTS: Hospitalized adults with severe COVID-19 pneumonia. INTERVENTIONS: Patients were randomized to receive IV astegolimab, efmarodocokin alfa, or placebo, plus standard of care. The primary endpoint was time to recovery, defined as time to a score of 1 or 2 on a 7-category ordinal scale by day 28. MEASUREMENTS AND MAIN RESULTS: The study randomized 396 patients. Median time to recovery was 11 days (hazard ratio [HR], 1.01 d; p = 0.93) and 10 days (HR, 1.15 d; p = 0.38) for astegolimab and efmarodocokin alfa, respectively, versus 10 days for placebo. Key secondary endpoints (improved recovery, mortality, or prevention of worsening) showed no treatment benefits. No new safety signals were observed and adverse events were similar across treatment arms. Biomarkers demonstrated that both drugs were pharmacologically active. CONCLUSIONS: Treatment with astegolimab or efmarodocokin alfa did not improve time to recovery in patients with severe COVID-19 pneumonia.