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

Julien Carvelli (1, 2, 3) , Ferhat Meziani (3) , Jean Dellamonica (4) , Pierre-Yves Cordier (5) , Jerome Allardet-Servent (6) , Megan Fraisse (7) , Lionel Velly (8, 9) , Saber Davide Barbar (10) , Samuel Lehingue (11) , Christophe Guervilly (8, 12) , Maxime Desgrouas (13) , Fabrice Camou (14, 15) , Christelle Piperoglou (2, 1) , Frederic Vely (2, 1) , Olivier Demaria (16) , Joyson Karakunnel (16) , Joanna Fares (16) , Luciana Batista (16) , Federico Rotolo (16) , Julien Viotti (16) , Agnes Boyer-Chammard (16) , Karine Lacombe (17) , Erwan Le Dault (18) , Michel Carles (4) , Nicolas Schleinitz (2, 1) , Eric Vivier (2, 16, 1)

1 TIMONE - Hôpital de la Timone [CHU - APHM]
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 Nouvel Hôpital Civil de Strasbourg
4 Hôpital l'Archet
5 Réanimation Polyvalente, HIA Laveran - Department of Intensive Care - Marseille
6 Hôpital Européen [Fondation Ambroise Paré - Marseille]
7 Centre Hospitalier Victor Dupouy
8 AMU - Aix Marseille Université
9 INT - Institut de Neurosciences de la Timone
10 Nîmes University Hospital, Department of Intensive Care
11 Hôpital Saint-Joseph [Marseille]
12 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
13 CHRO - Centre Hospitalier Régional d'Orléans
14 Hôpital Saint-André
15 UB - Université de Bordeaux
16 Innate Pharma
17 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
18 HIA Laveran a Marseille

OBJECTIVES: 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. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Spo 2 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. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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; p = 0.7) in cohort 1 and-0.28 (95% CI,-1.8 to 1.2; p = 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; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: 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).

Mots clés: avdoralimab; complement; COVID-19; inflammation; sepsis

Domaines: Sciences du Vivant [q-bio]

Julien Carvelli, Ferhat Meziani, Jean Dellamonica, Pierre-Yves Cordier, Jerome Allardet-Servent, et al.. Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE])*. Critical Care Medicine, 2022, 50, pp.1788 - 1798. ⟨10.1097/ccm.0000000000005683⟩. ⟨hal-03952765⟩