tetano
Editor, Senior Moderator
J Clin Invest
. 2021 Dec 6;e153173.
doi: 10.1172/JCI153173. Online ahead of print.
Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome
David S Perlin[SUP] 1 [/SUP], Garry A Neil[SUP] 2 [/SUP], Colleen Anderson[SUP] 3 [/SUP], Inbal Zafir-Lavie[SUP] 2 [/SUP], Shane Raines[SUP] 4 [/SUP], Carl F Ware[SUP] 5 [/SUP], H Jeffrey Wilkins[SUP] 6 [/SUP]
Affiliations
Abstract
Background: Severe coronavirus disease 2019 (COVID-19) infection is associated with a dysregulated immune response, which can result in cytokine release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT neutralization therapy.
Methods: This randomized, double-blind, multicenter, proof-of-concept trial enrolled adults hospitalized with COVID-19-associated pneumonia and mild to moderate ARDS. Patients received standard of care plus a single dose of CERC-002 or placebo. The primary endpoint was the proportion of patients receiving CERC-002 who remained alive and free of respiratory failure through day 28. Safety was assessed via adverse event monitoring.
Results: For most of the 83 enrolled patients, standard of care included systemic corticosteroids (88.0%) or remdesivir (57.8%). A higher proportion of patients remained alive and free of respiratory failure through day 28 after receiving CERC-002 (83.9%) versus placebo (64.5%; P = .044), including in patients ≥60 years (76.5% vs 47.1%, respectively; P = .042). Mortality rates were 7.7% (CERC-002) and 14.3% (placebo) at day 28 and 10.8% and 22.5%, respectively, at day 60. Treatment-emergent adverse events were less frequent with CERC-002 than placebo.
Conclusion: For patients with COVID-19-associated ARDS, adding CERC-002 to standard of care treatment reduces LIGHT levels and might reduce the risk of respiratory failure and death.
. 2021 Dec 6;e153173.
doi: 10.1172/JCI153173. Online ahead of print.
Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome
David S Perlin[SUP] 1 [/SUP], Garry A Neil[SUP] 2 [/SUP], Colleen Anderson[SUP] 3 [/SUP], Inbal Zafir-Lavie[SUP] 2 [/SUP], Shane Raines[SUP] 4 [/SUP], Carl F Ware[SUP] 5 [/SUP], H Jeffrey Wilkins[SUP] 6 [/SUP]
Affiliations
- PMID: 34871182
- DOI: 10.1172/JCI153173
Abstract
Background: Severe coronavirus disease 2019 (COVID-19) infection is associated with a dysregulated immune response, which can result in cytokine release syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19-associated ARDS have elevated free serum levels of the cytokine lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells (LIGHT; also known as TNFSF14). Such patients may benefit from LIGHT neutralization therapy.
Methods: This randomized, double-blind, multicenter, proof-of-concept trial enrolled adults hospitalized with COVID-19-associated pneumonia and mild to moderate ARDS. Patients received standard of care plus a single dose of CERC-002 or placebo. The primary endpoint was the proportion of patients receiving CERC-002 who remained alive and free of respiratory failure through day 28. Safety was assessed via adverse event monitoring.
Results: For most of the 83 enrolled patients, standard of care included systemic corticosteroids (88.0%) or remdesivir (57.8%). A higher proportion of patients remained alive and free of respiratory failure through day 28 after receiving CERC-002 (83.9%) versus placebo (64.5%; P = .044), including in patients ≥60 years (76.5% vs 47.1%, respectively; P = .042). Mortality rates were 7.7% (CERC-002) and 14.3% (placebo) at day 28 and 10.8% and 22.5%, respectively, at day 60. Treatment-emergent adverse events were less frequent with CERC-002 than placebo.
Conclusion: For patients with COVID-19-associated ARDS, adding CERC-002 to standard of care treatment reduces LIGHT levels and might reduce the risk of respiratory failure and death.