Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Intensive Care Medicine Année : 2021

Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial

Pierre-François Laterre
  • Fonction : Auteur
Peter Pickkers
  • Fonction : Auteur
Gernot Marx
  • Fonction : Auteur
Xavier Wittebole
  • Fonction : Auteur
Ferhat Meziani
  • Fonction : Auteur
  • PersonId : 1076640
Thierry Dugernier
  • Fonction : Auteur
Vincent Huberlant
  • Fonction : Auteur
Tobias Schuerholz
  • Fonction : Auteur
Bruno François
  • Fonction : Auteur
Jean-Baptiste Lascarrou
Albertus Beishuizen
  • Fonction : Auteur
Haikel Oueslati
  • Fonction : Auteur
Damien Contou
  • Fonction : Auteur
Oscar Hoiting
  • Fonction : Auteur
Jean-Claude Lacherade
  • Fonction : Auteur
Michael Bauer
  • Fonction : Auteur
Thomas Godet
  • Fonction : Auteur
Mahir Karakas
  • Fonction : Auteur
Julie Helms
  • Fonction : Auteur
Andreas Bergmann
  • Fonction : Auteur
Jens Zimmermann
  • Fonction : Auteur
Kathleen Richter
  • Fonction : Auteur
Oliver Hartmann
  • Fonction : Auteur
Melanie Pars
  • Fonction : Auteur

Résumé

PURPOSE: Investigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin. METHODS: Phase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality. RESULTS: 301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI -1.93-0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18-1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53-1.31, log-rank p = 0.44). CONCLUSIONS: Overall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients.

Dates et versions

hal-03944260 , version 1 (17-01-2023)

Identifiants

Citer

Pierre-François Laterre, Peter Pickkers, Gernot Marx, Xavier Wittebole, Ferhat Meziani, et al.. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Medicine, 2021, 47 (11), pp.1284-1294. ⟨10.1007/s00134-021-06537-5⟩. ⟨hal-03944260⟩
9 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More