Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
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
An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 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.
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Additional Info
Disclosure statements are available on the authors' profiles:
Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19: A Randomized Controlled Trial
Ann. Intern. Med 2022 Aug 09;[EPub Ahead of Print], C Barkauskas, E Mylonakis, G Poulakou, BE Young, DM Vock, L Siegel, N Engen, G Grandits, NR Mosaly, AM Vekstein, R Rogers, F Shehadeh, M Kaczynski, EK Mylona, KN Syrigos, V Rapti, DC Lye, D Shiau Hui, BBio, L Leither, KU Knowlton, MK Jain, R Marines-Price, A Osuji, JS Overcash, I Kalomenidis, Z Barmparessou, M Waters, K Zepeda, P Chen, S Torbati, F Kiweewa, N Sebudde, E Almasri, A Hughes, SR Bhagani, A Rodger, U Sandkovsky, RL Gottlieb, E Nnakelu, B Trautner, V Menon, J Lutaakome, M Matthay, P Robinson, K Protopapas, N Koulouris, I Kimuli, A Baduashvili, DL Braun, HF Günthard, S Ramachandruni, R Kidega, K Kim, TJ Hatlen, AN Phillips, DD Murray, TO Jensen, ML Padilla, EX Accardi, K Shaw-Saliba, RL Dewar, M Teitelbaum, V Natarajan, S Laverdure, HC Highbarger, MT Rehman, S Vogel, D Vallée, P Crew, N Atri, AJ Schechner, S Pett, F Hudson, J Badrock, G Touloumi, SM Brown, WH Self, CM North, AA Ginde, CC Chang, A Kelleher, S Nagy-Agren, S Vasudeva, D Looney, HH Nguyen, A Sánchez, AC Weintrob, B Grund, S Sharma, CS Reilly, R Paredes, A Bednarska, NP Gerry, AG Babiker, VJ Davey, AC Gelijns, ES Higgs, V Kan, G Matthews, BT Thompson, P Legenne, R Chandra, HC Lane, JD Neaton, and JD LundgrenFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This is a randomized placebo-controlled trial exploring the role of ensovibep in patients hospitalized with COVID-19. Ensovibep is part of a family of drugs called designed ankyrin repeat proteins (DARPins), which are a new class of engineered protein therapeutics designed to bind with high affinity and specificity to other proteins. Specifically, ensovibep was selected to bind the SARS-CoV-2 spike protein. While this was a negative study, it highlights the point that work is ongoing to find treatments for patients hospitalized with COVID-19.