Authors

Christina Barkauskas
Eleftherios Mylonakis
Garyfallia Poulakou
Barnaby E Young
David M Vock
Lianne Siegel
Nicole Engen
Greg Grandits
Nilima R Mosaly
Andrew M Vekstein
Ralph Rogers
Fadi Shehadeh
Matthew Kaczynski
Evangelia K Mylona
Konstantinos N Syrigos
Vasiliki Rapti
David C 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 Waters
Karla Zepeda
Peter Chen
Sam Torbati
Francis Kiweewa
Nicholus Sebudde
Eyad Almasri
Alyssa Hughes
Sanjay R Bhagani
Alison Rodger
Uriel Sandkovsky
Robert L Gottlieb
Eriobu Nnakelu
Barbara Trautner
Vidya Menon
Joseph Lutaakome
Michael Matthay
Philip Robinson
Konstantinos Protopapas
Nikolaos Koulouris
Ivan Kimuli
Amiran Baduashvili
Dominique L Braun
Huldrych F Günthard
Srikanth Ramachandruni
Robert Kidega
Kami Kim
Timothy J Hatlen
Andrew N Phillips
Daniel D Murray
Tomas O Jensen
Maria L Padilla
Evan X Accardi
Katy Shaw-Saliba
Robin L Dewar
Marc Teitelbaum
Ven Natarajan
Sylvain Laverdure
Helene C Highbarger
M Tauseef Rehman
Susan Vogel
David Vallée
Page Crew
Negin Atri
Adam J 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 Kelleher
Stephanie Nagy-Agren
Shikha Vasudeva
David Looney
Hien H Nguyen
Adriana Sánchez
Amy C Weintrob
Birgit Grund
Shweta Sharma
Cavan S Reilly
Roger Paredes
Agnieszka Bednarska
Norman P Gerry
Abdel G Babiker
Victoria J Davey
Annetine C Gelijns
Elizabeth S Higgs
Virginia Kan
Gail Matthews
B Taylor Thompson
Philippe Legenne
Richa Chandra
H Clifford Lane
James D Neaton
Jens D Lundgren

Publication Date

9-1-2022

Journal

Annals of Internal Medicine

DOI

10.7326/M22-1503

PMID

35939810

PMCID

PMC9384272

PubMedCentral® Posted Date

8-9-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

no

Keywords

Adult, Designed Ankyrin Repeat Proteins, Double-Blind Method, Humans, Recombinant Fusion Proteins, SARS-CoV-2, Treatment Outcome, COVID-19 Drug Treatment

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: 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 (

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.

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