Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19
ACTIV-3/TICO Study Group*, Christina Barkauskas, Eleftherios Mylonakis, Garyfallia Poulakou, Barnaby Edward Young, David M. Vock, Lianne Siegel, Nicole Engen, Greg Grandits, Nilima Mosaly, Andrew M. Vekstein, Ralph Rogers, Fadi Shehadeh, Matthew Kaczynski, Evangelia K. Mylona, Konstantinos N. Syrigos, Vasiliki Rapti, David Chien Lye, Diong Shiau Hui, Lindsay Leither, Kirk U. Knowlton, Mamta K. Jain, Rubria Marines-Price, Alice Osuji, J. Scott Overcash, Ioannis Kalomenidis, Zafeiria Barmparessou, Michael R. Waters, Karla Zepeda, Peter Chen, Sam Torbati, Francis Kiweewa, Nicholus Sebudde, Eyad Almasri, Alyssa Hughes, Sanjay Bhagani, Alison Rodger, Uriel Sandkovsky, Robert Gottlieb, Nnakelu Eriobu, Barbara W. Trautner, Vidya Menon, Joseph Lutaakome, Michael Matthay, Philip A. Robinson, Konstantinos Protopapas, Nikolaos Koulouris, Ivan Kimuli, Amiran Baduashvili, Dominique L. Braun, Huldrych F. Günthard, Srikanth Ramachandruni, Robert Kidega, Kami Kim, Timothy Hatlen, Andrew Phillips, Daniel D. Murray, Tomas Ø. Jensen, María L. Padilla, Evan X. Accardi, Katy Shaw-Saliba, Robin Dewar, Marc Teitelbaum, Ven Natarajan, Sylvain Laverdure, Helene C. Highbarger, M. Tauseef Rehman, Susan Vogel, David Vallée, Page Crew, Negin Atri, Adam Schechner, Sarah Pett, Fleur Hudson, Jonathan Badrock, Giota Touloumi, Samuel M. Brown, Wesley H. Self, Crystal M. North, Adit A. Ginde, Christina C. Chang, Anthony D. Kelleher, Stephanie Nagy-Agren, Shikha Vasudeva, David P. Looney, Hien Nguyen, Adriana Sánchez, Amy Weintrob, Birgit Grund, Shweta Sharma, Cavan Reilly, Roger Paredes, Agnieszka Bednarska, Norman P. Gerry, Abdel G. Babiker, Victoria J. Davey, Annetine C. Gelijns, Elizabeth S. Higgs, Virginia Kan, Gail Matthews
Abstract
BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.