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01-07-2020 | Septic Shock | Original

Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial

Authors: Bruno François, Xavier Wittebole, Ricard Ferrer, Jean-Paul Mira, Thierry Dugernier, Sébastien Gibot, Marc Derive, Aurélie Olivier, Valérie Cuvier, Stephan Witte, Peter Pickkers, François Vandenhende, Jean-Jacques Garaud, Miguel Sánchez, Margarita Salcedo-Magguilli, Pierre-François Laterre

Published in: Intensive Care Medicine | Issue 7/2020

Abstract

Purpose

Nangibotide is a specific TREM-1 inhibitor that tempered deleterious host–pathogens interactions, restored vascular function, and improved survival, in animal septic shock models. This study evaluated the safety and pharmacokinetics of nangibotide and its effects on clinical and pharmacodynamic parameters in septic shock patients.

Methods

This was a multicenter randomized, double-blind, two-stage study. Patients received either continuous infusion of nangibotide (0.3, 1.0, or 3.0 mg/kg/h) or placebo. Treatment began < 24 h after shock onset and continued for up to 5 days. Safety primary outcomes were adverse events (AEs), whether serious or not, and death. Exploratory endpoints evaluated nangibotide effects on pharmacodynamics, organ function, and mortality, and were analyzed according to baseline sTREM-1 concentrations.

Results

Forty-nine patients were randomized. All treatment emergent AEs (TEAEs) were collected until Day 28. No significant differences were observed in TEAEs between treatment groups. No drug withdrawal linked to TEAE nor appearance of anti-drug antibodies were reported. Nangibotide pharmacokinetics appeared to be dose-proportional and clearance was dose-independent. Nangibotide did not significantly affect pharmacodynamic markers. Decrease in SOFA score LS mean change (± SE) from baseline to Day 5 in pooled nangibotide groups versus placebo was − 0.7 (± 0.85) in the randomized population and − 1.5 (± 1.12) in patients with high baseline plasma sTREM-1 concentrations (non-significant). This pattern was similar to organ support end points.

Conclusion

No significant increases in TEAEs were detected in nangibotide-treated patients versus placebo. These results encourage further evaluation of nangibotide and further exploration of plasma sTREM-1 concentrations as a predictive efficacy biomarker.

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Title: Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial
Authors: Bruno François
Xavier Wittebole
Ricard Ferrer
Jean-Paul Mira
Thierry Dugernier
Sébastien Gibot
Marc Derive
Aurélie Olivier
Valérie Cuvier
Stephan Witte
Peter Pickkers
François Vandenhende
Jean-Jacques Garaud
Miguel Sánchez
Margarita Salcedo-Magguilli
Pierre-François Laterre
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keyword: Septic Shock
Published in: Intensive Care Medicine / Issue 7/2020
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-020-06109-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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