Journal Article

DKFZ-2026-00303

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Phase I Study Evaluating a Monoclonal Fc-Silenced SARS-CoV-2 Antibody in Patients With Moderate-to-Severe COVID-19.

Marconato, M. ; Hackenbruch, C. ; Jäger, S. ; Göpel, S. ; Кirieieva, T. ; Gavrylov, A. ; Fricke, H. ; Hust, M. ; Dübel, S. ; Dings, C. ; Lehr, T. ; Cuevas, M. ; Bitzer, M. ; Klein, C. ; Schwab, M.DKFZ* ; Wirtz, H. ; Schneider, J. ; Bitter, T. ; Frenzel, A. ; Dhaen, M.-A. ; Herrmann, A. ; Jung, G. ; Walz, J.DKFZ* ; Salih, H. R.DKFZ* ; Heitmann, J. S.

2026
Elsevier Science Amsterdam [u.a.]

Abstract: 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.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.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 IC50. 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.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).

Keyword(s): Antibody-dependent enhancement (ADE) ; COVID-19 ; Fc-silenced mAbs ; Monoclonal antibodies (mAbs) ; Phase I trial ; SARS-CoV-2

Note: #DKTKZFB26# / 2026 Mar;48(3):232-239

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Tübingen (TU01)
2. DKTK TU Translationale Immunologie (TU02)
3. DKTK TU AG Krebs-Immuntherapie (TU03)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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