TY - JOUR

T1 - Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19

T2 - A Randomized Controlled Trial

AU - Barkauskas, Christina

AU - Mylonakis, Eleftherios

AU - Poulakou, Garyfallia

AU - Young, Barnaby E

AU - Vock, David M

AU - Siegel, Lianne

AU - Engen, Nicole

AU - Grandits, Greg

AU - Mosaly, Nilima R

AU - Vekstein, Andrew M

AU - Rogers, Ralph

AU - Shehadeh, Fadi

AU - Kaczynski, Matthew

AU - Mylona, Evangelia K

AU - Syrigos, Konstantinos N

AU - Rapti, Vasiliki

AU - Lye, David C

AU - Hui, Diong Shiau

AU - Leither, Lindsay

AU - Knowlton, Kirk U

AU - Jain, Mamta K

AU - Marines-Price, Rubria

AU - Osuji, Alice

AU - Overcash, J Scott

AU - Kalomenidis, Ioannis

AU - Barmparessou, Zafeiria

AU - Waters, Michael

AU - Zepeda, Karla

AU - Chen, Peter

AU - Torbati, Sam

AU - Kiweewa, Francis

AU - Sebudde, Nicholus

AU - Almasri, Eyad

AU - Hughes, Alyssa

AU - Bhagani, Sanjay R

AU - Rodger, Alison

AU - Sandkovsky, Uriel

AU - Gottlieb, Robert L

AU - Nnakelu, Eriobu

AU - Trautner, Barbara

AU - Menon, Vidya

AU - Lutaakome, Joseph

AU - Matthay, Michael

AU - Robinson, Philip

AU - Protopapas, Konstantinos

AU - Koulouris, Nikolaos

AU - Kimuli, Ivan

AU - Baduashvili, Amiran

AU - Braun, Dominique L

AU - Lundgren, Jens D

AU - ACTIV-3/TICO Study Group

PY - 2022

Y1 - 2022

N2 - 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: 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.PRIMARY FUNDING SOURCE: National Institutes of Health.

AB - 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: 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.PRIMARY FUNDING SOURCE: National Institutes of Health.

KW - Adult

KW - Designed Ankyrin Repeat Proteins

KW - Double-Blind Method

KW - Humans

KW - Recombinant Fusion Proteins

KW - SARS-CoV-2

KW - Treatment Outcome

KW - COVID-19 Drug Treatment

U2 - 10.7326/M22-1503

DO - 10.7326/M22-1503

M3 - Journal article

C2 - 35939810

VL - 175

SP - 1266

EP - 1274

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 9

ER -