Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)

IMPORTANCE:. Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES:. This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal anti...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael Bauer, MD, Andreas Weyland, MD, Gernot Marx, MD, Frank Bloos, MD, PhD, Stephan Weber, Dipl. Stat., Norbert Weiler, MD, Stefan Kluge, MD, Anja Diers, MD, Tim Philipp Simon, MD, Ingmar Lautenschläger, MD, Matthias Gründling, MD, Ulrich Jaschinski, MD, Philipp Simon, MD, Axel Nierhaus, MD, Onnen Moerer, MD, Lorenz Reill, MD, Achim Jörres, MD, Renfeng Guo, MD, Markus Loeffler, MD, Konrad Reinhart, MD, Niels Riedemann, MD, for the SepNet-Study Group
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer 2021
Materias:	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
Acceso en línea:	https://doaj.org/article/425409c1c667424ab3c5530f15b92a63
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:425409c1c667424ab3c5530f15b92a63
record_format	dspace
spelling	oai:doaj.org-article:425409c1c667424ab3c5530f15b92a632021-11-25T07:56:59ZEfficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)2639-802810.1097/CCE.0000000000000577https://doaj.org/article/425409c1c667424ab3c5530f15b92a632021-11-01T00:00:00Zhttp://journals.lww.com/10.1097/CCE.0000000000000577https://doaj.org/toc/2639-8028IMPORTANCE:. Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES:. This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock. DESIGN:. Multicenter, randomized, and placebo-controlled study. SETTING AND PARTICIPANTS:. Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction. MAIN OUTCOMES AND MEASURES:. Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives. RESULTS:. Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups. CONCLUSIONS AND RELEVANCE:. Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.Michael Bauer, MDAndreas Weyland, MDGernot Marx, MDFrank Bloos, MD, PhDStephan Weber, Dipl. Stat.Norbert Weiler, MDStefan Kluge, MDAnja Diers, MDTim Philipp Simon, MDIngmar Lautenschläger, MDMatthias Gründling, MDUlrich Jaschinski, MDPhilipp Simon, MDAxel Nierhaus, MDOnnen Moerer, MDLorenz Reill, MDAchim Jörres, MDRenfeng Guo, MDMarkus Loeffler, MDKonrad Reinhart, MDNiels Riedemann, MDfor the SepNet-Study GroupWolters KluwerarticleMedical emergencies. Critical care. Intensive care. First aidRC86-88.9ENCritical Care Explorations, Vol 3, Iss 11, p e0577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9
spellingShingle	Medical emergencies. Critical care. Intensive care. First aid RC86-88.9 Michael Bauer, MD Andreas Weyland, MD Gernot Marx, MD Frank Bloos, MD, PhD Stephan Weber, Dipl. Stat. Norbert Weiler, MD Stefan Kluge, MD Anja Diers, MD Tim Philipp Simon, MD Ingmar Lautenschläger, MD Matthias Gründling, MD Ulrich Jaschinski, MD Philipp Simon, MD Axel Nierhaus, MD Onnen Moerer, MD Lorenz Reill, MD Achim Jörres, MD Renfeng Guo, MD Markus Loeffler, MD Konrad Reinhart, MD Niels Riedemann, MD for the SepNet-Study Group Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
description	IMPORTANCE:. Anaphylatoxin C5a, a proinflammatory complement split product, plays a central role in mediating organ dysfunction. OBJECTIVES:. This phase II clinical trial was conducted to study safety, tolerability, pharmacokinetics, and pharmacodynamics of vilobelimab, a recombinant monoclonal antibody against C5a, in patients with severe sepsis or septic shock. DESIGN:. Multicenter, randomized, and placebo-controlled study. SETTING AND PARTICIPANTS:. Eleven multidisciplinary ICUs across Germany. Adult patients with severe sepsis or septic shock and with early onset of infection-associated organ dysfunction. MAIN OUTCOMES AND MEASURES:. Patients were randomly assigned in a ratio of 2:1 to three subsequent dosing cohorts for IV vilobelimab or placebo receiving either 2 × 2 mg/kg (0 and 12 hr), 2 × 4 mg/kg (0 and 24 hr), and 3 × 4 mg/kg (0, 24, and 72 hr). Co-primary endpoints were pharmacodynamics (assessed by C5a concentrations), pharmacokinetics (assessed by vilobelimab concentrations), and safety of vilobelimab. Preliminary efficacy was evaluated by secondary objectives. RESULTS:. Seventy-two patients were randomized (16 patients for each vilobelimab dosing cohort and eight patients for each placebo dosing cohort). Vilobelimab application was associated with dosing dependent decrease in C5a compared with baseline (p < 0.001). Duration of C5a decrease increased with more frequent dosing. Membrane attack complex lysis capacity measured by 50% hemolytic complement was not affected. Vilobelimab was well tolerated with similar safety findings in all dose cohorts. No vilobelimab-specific adverse events emerged. For vilobelimab-treated patients, investigators attributed less treatment-emergent adverse events as related compared with placebo. Dosing cohorts 2 and 3 had the highest ICU-free and ventilator-free days. There was no difference in mortality, vasopressor-free days, or renal replacement therapy-free days between the groups. CONCLUSIONS AND RELEVANCE:. Administration of vilobelimab in patients with severe sepsis and septic shock selectively neutralizes C5a in a dose-dependent manner without blocking formation of the membrane attack complex and without resulting in detected safety issues. The data warrant further investigation of C5a inhibition in sepsis.
format	article
author	Michael Bauer, MD Andreas Weyland, MD Gernot Marx, MD Frank Bloos, MD, PhD Stephan Weber, Dipl. Stat. Norbert Weiler, MD Stefan Kluge, MD Anja Diers, MD Tim Philipp Simon, MD Ingmar Lautenschläger, MD Matthias Gründling, MD Ulrich Jaschinski, MD Philipp Simon, MD Axel Nierhaus, MD Onnen Moerer, MD Lorenz Reill, MD Achim Jörres, MD Renfeng Guo, MD Markus Loeffler, MD Konrad Reinhart, MD Niels Riedemann, MD for the SepNet-Study Group
author_facet	Michael Bauer, MD Andreas Weyland, MD Gernot Marx, MD Frank Bloos, MD, PhD Stephan Weber, Dipl. Stat. Norbert Weiler, MD Stefan Kluge, MD Anja Diers, MD Tim Philipp Simon, MD Ingmar Lautenschläger, MD Matthias Gründling, MD Ulrich Jaschinski, MD Philipp Simon, MD Axel Nierhaus, MD Onnen Moerer, MD Lorenz Reill, MD Achim Jörres, MD Renfeng Guo, MD Markus Loeffler, MD Konrad Reinhart, MD Niels Riedemann, MD for the SepNet-Study Group
author_sort	Michael Bauer, MD
title	Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
title_short	Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
title_full	Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
title_fullStr	Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
title_full_unstemmed	Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)
title_sort	efficacy and safety of vilobelimab (ifx-1), a novel monoclonal anti-c5a antibody, in patients with early severe sepsis or septic shock—a randomized, placebo-controlled, double-blind, multicenter, phase iia trial (sciens study)
publisher	Wolters Kluwer
publishDate	2021
url	https://doaj.org/article/425409c1c667424ab3c5530f15b92a63
work_keys_str_mv	AT michaelbauermd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT andreasweylandmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT gernotmarxmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT frankbloosmdphd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT stephanweberdiplstat efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT norbertweilermd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT stefanklugemd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT anjadiersmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT timphilippsimonmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT ingmarlautenschlagermd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT matthiasgrundlingmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT ulrichjaschinskimd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT philippsimonmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT axelnierhausmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT onnenmoerermd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT lorenzreillmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT achimjorresmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT renfengguomd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT markusloefflermd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT konradreinhartmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT nielsriedemannmd efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy AT forthesepnetstudygroup efficacyandsafetyofvilobelimabifx1anovelmonoclonalantic5aantibodyinpatientswithearlyseveresepsisorsepticshockarandomizedplacebocontrolleddoubleblindmulticenterphaseiiatrialsciensstudy
_version_	1718413613942702080

Efficacy and Safety of Vilobelimab (IFX-1), a Novel Monoclonal Anti-C5a Antibody, in Patients With Early Severe Sepsis or Septic Shock—A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase IIa Trial (SCIENS Study)

Ejemplares similares