Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19

Roberto Caricchio, Antonio Abbate, Ivan Gordeev, Jamie Meng, Priscilla Y Hsue, Tuhina Neogi, Roberto Arduino, Daria Fomina, Roman Bogdanov, Tatiana Stepanenko, Pilar Ruiz-Seco, Andrés Gónzalez-García, Yu Chen, Yuhan Li, Sarah Whelan, Stephanie Noviello, Stanislas Faguer, Alberto Papi, Fabiano Di Marco, Alina S. Agafina, Anastasia S. Mochalova, Dmitry A. Lioznov, Dmitry V. Privalov, Konstantin V. Trufanov, Tatiana I. Martynenko, José Luis Pablos-Alvarez, Segundo Bujan, Vicente Estrada, Xavier Solanich-Moreno, Harpal Randeva, Hasan Tahir, Helen J. Lachmann, Sinisa Savic, Vishal Patel, Anne Lachiewicz, Babafemi Taiwo, Daniel R. Kuritzkes, Jeffrey M. Jacobson, Joel V. Chua, Mihran Shirinian, Monica Fung, Turner Overton, Vinay Malhotra, Eugene Kissin, Natalia Morone, Manish Sagar, Marcin Trojanowski, Parag Desai, Samuel Krachman, Daniel Salerno, Jeffrey Stewart, Matthew Zheng, Rohit Gupta, Kartik Shenoy, Nathaniel Marchetti, Maulin Patel, Fredric Jaffe, Junad Chowdhury, James Brown, Maria Elena Vega-Sanchez, Stephen Codella, Steven Verga, Gustavo Fernandez-Romero, Janpreet Mokha, Gerard J. Criner, Parth Rali, Sameep Sehgal, Zachariah Dorey-Stein, Aditi Satti, Eduardo Dominguez-Castillo, Nicole Mills, Albert J. Mamary, Andrew Gangemi, Jacob Shani, Robert Frankel, Kavita Sharma, Yury Malyshev, Jason Brady, Manan Christian, Gwendolyn Tan-Augenstein, Damian A. Chiandussi, Ann Behne, Mellisa Black, Aldo Bonaventura, Rick Earl Clary, Henley Deutsch, Christina Duke, Joan Greer, Mary Hardin, Mary Harmon, Heather Kemp, Ai-Chen Ho, Ikenna Ibe, Amy Ladd, Amr Marawan, Roshanak Markley, Kim McKee, Virginia Mihalick, Alison Montpetit, James Mbualungu, Joyce O’Brien, Catherine Owen, Mary Pak, Nimesh Patel, William Payne, Anna Priday, Robin Sculthorpe, Melissa Sears, Yub Raj Sedhai, Earl Kenneth Sims, Kathryn Spence, Hilary Tackett, Georgia Thomas, Juanita Turner, Benjamin Van Tassell, Alessandra Vecchiè, George Wohlford

Effective treatments for patients with severe COVID-19 are needed. To evaluate the efficacy of canakinumab, an anti-interleukin-1β antibody, in patients hospitalized with severe COVID-19. This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. ClinicalTrials.gov Identifier: NCT04362813.