PMID- 32468087
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1432-1238 (Electronic)
IS  - 0342-4642 (Linking)
VI  - 46
IP  - 7
DP  - 2020 Jul
TI  - Nangibotide in patients with septic shock: a Phase 2a randomized controlled 
      clinical trial.
PG  - 1425-1437
LID - 10.1007/s00134-020-06109-z [doi]
AB  - 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.
FAU - Francois, Bruno
AU  - Francois B
AUID- ORCID: 0000-0002-2531-1652
AD  - Medical-Surgical ICU Department and Inserm CIC1435 & UMR1092, CRICS-TRIGGERSEP 
      Network, CHU Limoges, Limoges, France. b.francois@unilim.fr.
FAU - Wittebole, Xavier
AU  - Wittebole X
AD  - Department of Critical Care Medicine, St Luc University Hospital, Universite 
      Catholique de Louvain, Brussels, Belgium.
FAU - Ferrer, Ricard
AU  - Ferrer R
AD  - ICU Department, Vall d'Hebron University Hospital, Barcelona, Spain.
FAU - Mira, Jean-Paul
AU  - Mira JP
AD  - Medical ICU, Cochin Hotel-Dieu, AP-HP, Paris, France.
FAU - Dugernier, Thierry
AU  - Dugernier T
AD  - ICU Department, Clinique St. Pierre, Ottignies, Belgium.
FAU - Gibot, Sebastien
AU  - Gibot S
AD  - Medical ICU Department, Hospital Central, CHU Nancy, Nancy, France.
AD  - Inserm U1116, Nancy Medical Faculty, Lorraine University, Nancy , France.
FAU - Derive, Marc
AU  - Derive M
AD  - Inotrem SA, Paris, France.
FAU - Olivier, Aurelie
AU  - Olivier A
AD  - Inotrem SA, Paris, France.
FAU - Cuvier, Valerie
AU  - Cuvier V
AD  - Inotrem SA, Paris, France.
FAU - Witte, Stephan
AU  - Witte S
AD  - Helion Pharma, Schriesheim, Germany.
FAU - Pickkers, Peter
AU  - Pickkers P
AD  - ICU Department, Radboudumc Hospital, Nijmegen, The Netherlands.
FAU - Vandenhende, Francois
AU  - Vandenhende F
AD  - ClinBay SPRL, Baisy-Thy, Belgium.
FAU - Garaud, Jean-Jacques
AU  - Garaud JJ
AD  - Inotrem SA, Paris, France.
FAU - Sanchez, Miguel
AU  - Sanchez M
AD  - ICU Department, Hospital Clinico San Carlos, Madrid, Spain.
FAU - Salcedo-Magguilli, Margarita
AU  - Salcedo-Magguilli M
AD  - Inotrem SA, Paris, France.
FAU - Laterre, Pierre-Francois
AU  - Laterre PF
AD  - Department of Critical Care Medicine, St Luc University Hospital, Universite 
      Catholique de Louvain, Brussels, Belgium.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20200528
PL  - United States
TA  - Intensive Care Med
JT  - Intensive care medicine
JID - 7704851
RN  - 0 (Immunologic Factors)
SB  - IM
MH  - Animals
MH  - Double-Blind Method
MH  - Humans
MH  - Immunologic Factors
MH  - *Shock, Septic/drug therapy
MH  - Treatment Outcome
OTO - NOTNLM
OT  - LR12
OT  - Nangibotide
OT  - Septic shock
OT  - TREM-1
EDAT- 2020/05/30 06:00
MHDA- 2021/04/28 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/02/10 00:00 [received]
PHST- 2020/05/11 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - 10.1007/s00134-020-06109-z [pii]
AID - 10.1007/s00134-020-06109-z [doi]
PST - ppublish
SO  - Intensive Care Med. 2020 Jul;46(7):1425-1437. doi: 10.1007/s00134-020-06109-z. 
      Epub 2020 May 28.