Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Autor:	Barkauskas C; Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Duke Health, Durham, North Carolina., Mylonakis E; Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island., Poulakou G; 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece., Young BE; National Centre for Infectious Diseases, Singapore., Vock DM; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Siegel L; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Engen N; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Grandits G; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Mosaly NR; Duke University Hospital, Durham, North Carolina., Vekstein AM; Duke University Hospital, Durham, North Carolina., Rogers R; Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island., Shehadeh F; Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island., Kaczynski M; Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island., Mylona EK; Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island., Syrigos KN; 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece., Rapti V; 3rd Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece., Lye DC; National Centre for Infectious Diseases, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Singapore., Hui DS; National Centre for Infectious Diseases, Tan Tock Seng Hospital, Singapore., Leither L; Division of Pulmonary and Critical Care, Department of Medicine, Intermountain Medical Center, Salt Lake City, Utah., Knowlton KU; Cardiovascular Department, Intermountain Medical Center, Salt Lake City, Utah., Jain MK; UT Southwestern Medical Center and Parkland Health and Hospital Systems, Dallas, Texas., Marines-Price R; UT Southwestern Medical Center and Parkland Health and Hospital Systems, Dallas, Texas., Osuji A; UT Southwestern Medical Center and Parkland Health and Hospital Systems, Dallas, Texas., Overcash JS; Velocity San Diego, San Diego, California., Kalomenidis I; 1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evaggelismos General Hospital, Athens, Greece., Barmparessou Z; 1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evaggelismos General Hospital, Athens, Greece., Waters M; Velocity Chula Vista, San Diego, California., Zepeda K; Velocity Chula Vista, San Diego, California., Chen P; Cedars-Sinai Medical Center, Los Angeles, California., Torbati S; Cedars-Sinai Medical Center, Los Angeles, California., Kiweewa F; Lira Regional Referral Hospital, Lira, Uganda., Sebudde N; Lira Regional Referral Hospital, Lira, Uganda., Almasri E; University of California, San Francisco-Fresno, Fresno, California., Hughes A; University of California, San Francisco-Fresno, Fresno, California., Bhagani SR; Royal Free Hospital, London, England., Rodger A; Royal Free Hospital, London, England., Sandkovsky U; Baylor Scott & White Health, Dallas, Texas., Gottlieb RL; Baylor Scott & White Health, Dallas, Texas., Nnakelu E; Institute of Human Virology Nigeria, Abuja, Nigeria., Trautner B; Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas., Menon V; NYC Health + Hospitals/Lincoln, Bronx, New York., Lutaakome J; Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda., Matthay M; University of California, San Francisco, Medical Center, Fresno, California., Robinson P; Hoag Memorial Hospital Presbyterian, Newport Beach, California., Protopapas K; 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece., Koulouris N; 1st Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece., Kimuli I; Makerere University Lung Institute, Kampala, Uganda., Baduashvili A; Division of Hospital Medicine, University of Colorado Hospital - Anschutz Medical Campus, Aurora, Colorado., Braun DL; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Günthard HF; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and Institute of Medical Virology, University of Zurich, Zurich, Switzerland., Ramachandruni S; CHRISTUS Spohn Shoreline Hospital, Corpus Christi, Texas., Kidega R; Gulu Regional Referral Hospital, Gulu, Uganda., Kim K; Division of Infectious Diseases, University of South Florida and Global Emerging Diseases Institute, Tampa General Hospital, Tampa, Florida., Hatlen TJ; Lundquist Institute for Biomedical Innovation, Torrance, California., Phillips AN; Institute for Global Health, University College London, England., Murray DD; CHIP Center of Excellence for Health, Immunity, and Infections and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark., Jensen TO; CHIP Center of Excellence for Health, Immunity, and Infections and Department of Infectious Diseases, Rigshospitalet, Copenhagen, and Department of Pulmonary and Infectious Diseases, North Zealand University Hospital, Hillerod, Denmark., Padilla ML; Icahn School of Medicine at Mount Sinai, New York, New York., Accardi EX; Icahn School of Medicine at Mount Sinai, New York, New York., Shaw-Saliba K; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland., Dewar RL; Frederick National Laboratory for Cancer Research, Frederick, Maryland., Teitelbaum M; Leidos Biomedical Research, Frederick, Maryland., Natarajan V; Frederick National Laboratory for Cancer Research, Frederick, Maryland., Laverdure S; Laboratory of Human Retrovirology and Immunoinformatics, National Institutes of Health, Frederick, Maryland., Highbarger HC; Frederick National Laboratory for Cancer Research, Frederick, Maryland., Rehman MT; Frederick National Laboratory for Cancer Research, Frederick, Maryland., Vogel S; Office of Clinical Research Policy and Regulatory Operations, National Institutes of Health, Bethesda, Maryland., Vallée D; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Crew P; Collaborative Clinical Research Branch, National Institutes of Health, Bethesda, Maryland., Atri N; Office of Clinical Research Policy and Regulatory Operations, National Institutes of Health, Bethesda, Maryland., Schechner AJ; Leidos Biomedical Research, Frederick, Maryland., Pett S; The Medical Research Council Clinical Trials Unit at University College London, London, England., Hudson F; The Medical Research Council Clinical Trials Unit at University College London, London, England., Badrock J; The Medical Research Council Clinical Trials Unit at University College London, London, England., Touloumi G; Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Brown SM; Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center, and Department of Internal Medicine, University of Utah, Murray, Utah., Self WH; Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., North CM; Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Ginde AA; University of Colorado School of Medicine, Aurora, Colorado., Chang CC; The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia., Kelleher A; The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia., Nagy-Agren S; Salem Veterans Affairs Medical Center, Salem, Virginia., Vasudeva S; Salem Veterans Affairs Medical Center, Salem, Virginia., Looney D; The Veterans Medical Research Foundation, San Diego, California., Nguyen HH; Veterans Affairs Northern California Health Care System, Sacramento, California., Sánchez A; Washington Veterans Affairs Medical Center, Washington, DC., Weintrob AC; Infectious Diseases Section, Washington Veterans Affairs Medical Center, Washington, DC., Grund B; School of Statistics, University of Minnesota, Minneapolis, Minnesota., Sharma S; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Reilly CS; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Paredes R; Hospital Universitari Germans Trias i Pujol, Badalona, Spain., Bednarska A; Wojewódzki Szpital Zakaźny w Warszawie, Medical University of Warsaw, Warsaw, Poland., Gerry NP; Advanced Biomedical Laboratories, Cinnaminson, New Jersey., Babiker AG; The Medical Research Council Clinical Trials Unit at University College London, London, England., Davey VJ; U.S. Department of Veterans Affairs, Washington, DC., Gelijns AC; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York., Higgs ES; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland., Kan V; Infectious Diseases Section, Veterans Affairs Medical Center, Washington, DC., Matthews G; The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia., Thompson BT; Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts., Legenne P; Molecular Partners, Zurich, Switzerland., Chandra R; Novartis, East Hanover Township, New Jersey., Lane HC; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland., Neaton JD; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota., Lundgren JD; CHIP Center of Excellence for Health, Immunity, and Infections and Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Annals of internal medicine [Ann Intern Med] 2022 Sep; Vol. 175 (9), pp. 1266-1274. Date of Electronic Publication: 2022 Aug 09.
DOI:	10.7326/M22-1503
Abstrakt:	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.
Databáze:	MEDLINE
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