tetano
Editor, Senior Moderator
Clin Ther
. 2026 Feb 6:S0149-2918(26)00007-X.
doi: 10.1016/j.clinthera.2026.01.004. Online ahead of print.
Phase I Study Evaluating a Monoclonal Fc-Silenced SARS-CoV-2 Antibody in Patients With Moderate-to-Severe COVID-19
Maddalena Marconato[SUP] 1 [/SUP], Christopher Hackenbruch[SUP] 2 [/SUP], Simon Jäger[SUP] 3 [/SUP], Siri Göpel[SUP] 4 [/SUP], Tetiana Кirieieva[SUP] 5 [/SUP], Anatoliy Gavrylov[SUP] 6 [/SUP], Harald Fricke[SUP] 7 [/SUP], Michael Hust[SUP] 8 [/SUP], Stefan Dübel[SUP] 9 [/SUP], Christiane Dings[SUP] 10 [/SUP], Thorsten Lehr[SUP] 11 [/SUP], Mandy Cuevas[SUP] 12 [/SUP], Michael Bitzer[SUP] 4 [/SUP], Constantin Klein[SUP] 4 [/SUP], Matthias Schwab[SUP] 13 [/SUP], Hubert Wirtz[SUP] 14 [/SUP], Jochen Schneider[SUP] 15 [/SUP], Thomas Bitter[SUP] 16 [/SUP], André Frenzel[SUP] 7 [/SUP], Marie-Ann Dhaen[SUP] 7 [/SUP], Andreas Herrmann[SUP] 7 [/SUP], Gundram Jung[SUP] 17 [/SUP], Juliane S Walz[SUP] 18 [/SUP], Helmut R Salih[SUP] 19 [/SUP], Jonas S Heitmann[SUP] 20 [/SUP]
Affiliations
Purpose: The evolution of Severe Acute Respiratory Syndrome Coronavirus 2 challenged the effectiveness of vaccines, while monoclonal antibodies (mAbs) were discontinued due to emergent resistance. This study evaluated the safety and explored the preliminary efficacy of COR-101, a novel mAb with a silenced Fc region designed to minimize antibody-dependent enhancement in hospitalized patients with moderate-to-severe disease.
Methods: Thirty-three participants were enrolled across Germany and Ukraine in a randomized, double-blind, placebo-controlled Phase Ib/II trial. Patients received either a single dose of COR-101, or placebo, as add-on therapy to the standard of care.
Findings: COR-101 was well tolerated, with no treatment-related severe adverse events (AEs), grade ≥3 AEs, or acute infusion reactions. Four unrelated severe AEs were observed, and 2 patients died due to coronavirus disease 2019. COR-101 showed dose-proportional pharmacokinetics, long half-life, and serum concentrations above IC[SUB]50[/SUB]. Patients were treated in different dose groups, and in exploratory analysis, viral clearance was observed at day 28 in 80%, 55.6%, 16.7%, and 42.9% of patients in the 4.0, 10.0, 25.0 mg/kg, and placebo groups, respectively. The predominant virus variant changed from alpha to delta and omicron, resulting in reduced in vitro neutralization, potentially explaining the observed reduced efficacy.
Implications: COR-101 demonstrated a favorable safety profile, but exploratory data showed limited efficacy against omicron, highlighting the tolerability of Fc-silenced mAbs and the need for adaptive therapeutic strategies against rapidly evolving viral pathogens (ClinicalTrials.gov identifier: NCT04674566).
Keywords: Antibody-dependent enhancement (ADE); COVID-19; Fc-silenced mAbs; Monoclonal antibodies (mAbs); Phase I trial; SARS-CoV-2.
. 2026 Feb 6:S0149-2918(26)00007-X.
doi: 10.1016/j.clinthera.2026.01.004. Online ahead of print.
Phase I Study Evaluating a Monoclonal Fc-Silenced SARS-CoV-2 Antibody in Patients With Moderate-to-Severe COVID-19
Maddalena Marconato[SUP] 1 [/SUP], Christopher Hackenbruch[SUP] 2 [/SUP], Simon Jäger[SUP] 3 [/SUP], Siri Göpel[SUP] 4 [/SUP], Tetiana Кirieieva[SUP] 5 [/SUP], Anatoliy Gavrylov[SUP] 6 [/SUP], Harald Fricke[SUP] 7 [/SUP], Michael Hust[SUP] 8 [/SUP], Stefan Dübel[SUP] 9 [/SUP], Christiane Dings[SUP] 10 [/SUP], Thorsten Lehr[SUP] 11 [/SUP], Mandy Cuevas[SUP] 12 [/SUP], Michael Bitzer[SUP] 4 [/SUP], Constantin Klein[SUP] 4 [/SUP], Matthias Schwab[SUP] 13 [/SUP], Hubert Wirtz[SUP] 14 [/SUP], Jochen Schneider[SUP] 15 [/SUP], Thomas Bitter[SUP] 16 [/SUP], André Frenzel[SUP] 7 [/SUP], Marie-Ann Dhaen[SUP] 7 [/SUP], Andreas Herrmann[SUP] 7 [/SUP], Gundram Jung[SUP] 17 [/SUP], Juliane S Walz[SUP] 18 [/SUP], Helmut R Salih[SUP] 19 [/SUP], Jonas S Heitmann[SUP] 20 [/SUP]
Affiliations
- PMID: 41654452
- DOI: 10.1016/j.clinthera.2026.01.004
Purpose: The evolution of Severe Acute Respiratory Syndrome Coronavirus 2 challenged the effectiveness of vaccines, while monoclonal antibodies (mAbs) were discontinued due to emergent resistance. This study evaluated the safety and explored the preliminary efficacy of COR-101, a novel mAb with a silenced Fc region designed to minimize antibody-dependent enhancement in hospitalized patients with moderate-to-severe disease.
Methods: Thirty-three participants were enrolled across Germany and Ukraine in a randomized, double-blind, placebo-controlled Phase Ib/II trial. Patients received either a single dose of COR-101, or placebo, as add-on therapy to the standard of care.
Findings: COR-101 was well tolerated, with no treatment-related severe adverse events (AEs), grade ≥3 AEs, or acute infusion reactions. Four unrelated severe AEs were observed, and 2 patients died due to coronavirus disease 2019. COR-101 showed dose-proportional pharmacokinetics, long half-life, and serum concentrations above IC[SUB]50[/SUB]. Patients were treated in different dose groups, and in exploratory analysis, viral clearance was observed at day 28 in 80%, 55.6%, 16.7%, and 42.9% of patients in the 4.0, 10.0, 25.0 mg/kg, and placebo groups, respectively. The predominant virus variant changed from alpha to delta and omicron, resulting in reduced in vitro neutralization, potentially explaining the observed reduced efficacy.
Implications: COR-101 demonstrated a favorable safety profile, but exploratory data showed limited efficacy against omicron, highlighting the tolerability of Fc-silenced mAbs and the need for adaptive therapeutic strategies against rapidly evolving viral pathogens (ClinicalTrials.gov identifier: NCT04674566).
Keywords: Antibody-dependent enhancement (ADE); COVID-19; Fc-silenced mAbs; Monoclonal antibodies (mAbs); Phase I trial; SARS-CoV-2.