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Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.
Skendros, Panagiotis; Germanidis, Georgios; Mastellos, Dimitrios C; Antoniadou, Christina; Gavriilidis, Efstratios; Kalopitas, Georgios; Samakidou, Anna; Liontos, Angelos; Chrysanthopoulou, Akrivi; Ntinopoulou, Maria; Kogias, Dionysios; Karanika, Ioanna; Smyrlis, Andreas; Cepaityte, Dainora; Fotiadou, Iliana; Zioga, Nikoleta; Mitroulis, Ioannis; Gatselis, Nikolaos K; Papagoras, Charalampos; Metallidis, Simeon; Milionis, Haralampos; Dalekos, George N; Willems, Loek; Persson, Barbro; Manivel, Vivek Anand; Nilsson, Bo; Connolly, E Sander; Iacobelli, Simona; Papadopoulos, Vasileios; Calado, Rodrigo T; Huber-Lang, Markus; Risitano, Antonio M; Yancopoulou, Despina; Ritis, Konstantinos; Lambris, John D.
  • Skendros P; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Germanidis G; First Department of Internal Medicine, AHEPA University Hospital, and Basic and Translational Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Mastellos DC; National Center for Scientific Research "Demokritos", Athens, Greece.
  • Antoniadou C; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Gavriilidis E; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Kalopitas G; First Department of Internal Medicine, AHEPA University Hospital, and Basic and Translational Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Samakidou A; Department of Medicine and Research Laboratory of Internal Medicine, National and European Expertise Center of Greece in Autoimmune Liver Diseases (ERN Rare-Liver), General University Hospital of Larissa, Larissa, Greece.
  • Liontos A; Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
  • Chrysanthopoulou A; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Ntinopoulou M; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Kogias D; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Karanika I; First Department of Internal Medicine, AHEPA University Hospital, and Basic and Translational Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Smyrlis A; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Cepaityte D; First Department of Internal Medicine, AHEPA University Hospital, and Basic and Translational Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Fotiadou I; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Zioga N; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Mitroulis I; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Gatselis NK; Department of Medicine and Research Laboratory of Internal Medicine, National and European Expertise Center of Greece in Autoimmune Liver Diseases (ERN Rare-Liver), General University Hospital of Larissa, Larissa, Greece.
  • Papagoras C; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Metallidis S; First Department of Internal Medicine, AHEPA University Hospital, and Basic and Translational Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Milionis H; Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.
  • Dalekos GN; Department of Medicine and Research Laboratory of Internal Medicine, National and European Expertise Center of Greece in Autoimmune Liver Diseases (ERN Rare-Liver), General University Hospital of Larissa, Larissa, Greece.
  • Willems L; R&D Department, Hycult Biotechnology, Uden, Netherlands.
  • Persson B; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Manivel VA; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Nilsson B; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Connolly ES; Department of Neurological Surgery, Columbia University, New York, NY, USA.
  • Iacobelli S; Department of Biology, University of Rome Tor Vergata, Rome, Italy.
  • Papadopoulos V; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Calado RT; Department of Medical Imaging, Hematology and Oncology, University of São Paulo, School of Medicine, Ribeirão Preto, Brazil.
  • Huber-Lang M; Institute for Clinical and Experimental Trauma-Immunology, Ulm University Hospital, Ulm, Germany.
  • Risitano AM; AORN Moscati Avellino, Italy and Federico II University of Naples, Naples, Italy.
  • Yancopoulou D; Amyndas Pharmaceuticals, Glyfada, Greece.
  • Ritis K; First Department of Internal Medicine and Laboratory of Molecular Hematology, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • Lambris JD; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Sci Adv ; 8(33): eabo2341, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-1992928
ABSTRACT
Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 (n = 16) or placebo (n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Randomized controlled trials Language: English Journal: Sci Adv Year: 2022 Document Type: Article Affiliation country: Sciadv.abo2341

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Randomized controlled trials Language: English Journal: Sci Adv Year: 2022 Document Type: Article Affiliation country: Sciadv.abo2341