Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE])

DOI record: { "DOI": "10.1097/ccm.0000000000005683", "ISSN": [ "0090-3493" ], "URL": "http://dx.doi.org/10.1097/CCM.0000000000005683", "abstract": "<jats:sec>\n <jats:title>OBJECTIVES:</jats:title>\n <jats:p>Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>DESIGN:</jats:title>\n <jats:p>FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>SETTING:</jats:title>\n <jats:p>Twelve clinical sites in France (ICU and general hospitals).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>PATIENTS:</jats:title>\n <jats:p>Patients receiving greater than or equal to 5 L oxygen/min to maintain Sp<jats:sc>o</jats:sc>\n <jats:sub>2</jats:sub> greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>INTERVENTIONS:</jats:title>\n <jats:p>Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>MEASUREMENTS AND MAIN RESULTS:</jats:title>\n <jats:p>We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of –0.26 (95% CI, –1.2 to 0.7; <jats:italic toggle=\"yes\">p</jats:italic> = 0.7) in cohort 1 and –0.28 (95% CI, –1.8 to 1.2; <jats:italic toggle=\"yes\">p</jats:italic> = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of –6.3 (95% CI, –13.2 to 0.7; <jats:italic toggle=\"yes\">p</jats:italic> = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>CONCLUSIONS:</jats:title>\n <jats:p>In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).</jats:p>\n </jats:sec>", "author": [ { "affiliation": [], "family": "Carvelli", "given": "Julien", "sequence": "first" }, { "affiliation": [ { "name": "Department of Intensive Care, Médecine Intensive & Réanimation, Nouvel Hôpital Civil, Strasbourg University Hospital, INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg University, Strasbourg, France." } ], "family": "Meziani", "given": "Ferhat", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Medecine Intensive & Reanimation, Hôpital l’Archet 1, Nice University Hospital, Cote d’Azur University, UR2CA, Nice, France." } ], "family": "Dellamonica", "given": "Jean", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Réanimation Polyvalente, HIA Laveran, Marseille, France." } ], "family": "Cordier", "given": "Pierre-Yves", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Hôpital Européen, Marseille, France." } ], "family": "Allardet-Servent", "given": "Jerome", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France." } ], "family": "Fraisse", "given": "Megan", "sequence": "additional" }, { "affiliation": [ { "name": "Aix-Marseille University, Marseille, France." }, { "name": "AP-HM, Department of Anesthesiology & Critical Care Medicine, Réanimation Polyvalente, Timone University Hospital, Institut Neuroscience Timone CNRS UMR-7289, Marseille, France." } ], "family": "Velly", "given": "Lionel", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Nîmes University Hospital, University of Montpellier, Nîmes, France." } ], "family": "Barbar", "given": "Saber Davide", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Hôpital Saint-Joseph, Marseille, France." } ], "family": "Lehingue", "given": "Samuel", "sequence": "additional" }, { "affiliation": [ { "name": "Aix-Marseille University, Marseille, France." }, { "name": "AP-HM, Department of Intensive Care, Médecine Intensive Réanimation, North Hospital, Centre d’Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279Marseille, Marseille, France." } ], "family": "Guervilly", "given": "Christophe", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Medecine Intensive & Reanimation, Centre Hospitalier Régional d’Orléans, Orléans, France." } ], "family": "Desgrouas", "given": "Maxime", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Intensive Care, Bordeaux University Hospital, Hôpital Saint-André, University of Bordeaux, Bordeaux, France." } ], "family": "Camou", "given": "Fabrice", "sequence": "additional" }, { "affiliation": [ { "name": "Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France." }, { "name": "AP-HM, Timone University Hospital, Immunology, Marseille, France." } ], "family": "Piperoglou", "given": "Christelle", "sequence": "additional" }, { "affiliation": [ { "name": "Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France." }, { "name": "Aix-Marseille University, Marseille, France." }, { "name": "AP-HM, Timone University Hospital, Immunology, Marseille, France." } ], "family": "Vely", "given": "Frederic", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Demaria", "given": "Olivier", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Karakunnel", "given": "Joyson", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Fares", "given": "Joanna", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Batista", "given": "Luciana", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Rotolo", "given": "Federico", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Viotti", "given": "Julien", "sequence": "additional" }, { "affiliation": [ { "name": "Innate Pharma, Marseille, France." } ], "family": "Boyer-Chammard", "given": "Agnes", "sequence": "additional" }, { "affiliation": [ { "name": "AP-HP, Tropical Medicine & Infectious Diseases, Saint-Antoine Univeristy Hospital, Sorbonne University, Inserm UMR-S1136 IPLESP, Paris, France." } ], "family": "Lacombe", "given": "Karine", "sequence": "additional" }, { "affiliation": [ { "name": "Tropical Medicine & Infectious Diseases, HIA Laveran, Marseille, France." } ], "family": "Le Dault", "given": "Erwan", "sequence": "additional" }, { "affiliation": [ { "name": "Tropical Medicine & Infectious Diseases, Hôpital l’Archet 1, Nice Univeristy Hospital, Université Côte d’Azur, Inserm-C3M, Nice, France." } ], "family": "Carles", "given": "Michel", "sequence": "additional" }, { "affiliation": [ { "name": "Marseille Immunopôle, Timone University Hospital, CNRS, INSERM, CIML, Marseille, France." }, { "name": "Aix-Marseille University, Marseille, France." }, { "name": "AP-HM, Internal Medicine Department, Timone University Hospital, Marseille, France." } ], "family": "Schleinitz", "given": "Nicolas", "sequence": "additional" }, { "affiliation": [ { "name": "Marseille Immunopôle, Timone University 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