Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases

Abstract : OBJECTIVE: No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. DESIGN: double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. RESULTS: 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). CONCLUSION: ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH.
Liste complète des métadonnées

https://hal.umontpellier.fr/hal-01872887
Contributeur : Cécile Nowak <>
Soumis le : mercredi 26 mai 2021 - 15:54:31
Dernière modification le : vendredi 11 juin 2021 - 16:02:02
Archivage à long terme le : : vendredi 27 août 2021 - 20:16:19

Fichier

pone.0150733.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

Bertrand Nalpas, Philippe Ichai, Laure Jamot, Nicolas Carbonell, Marika Rudler, et al.. A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases. PLoS ONE, Public Library of Science, 2016, 11 (3), pp.e0150733. ⟨10.1371/journal.pone.0150733⟩. ⟨hal-01872887⟩

Partager

Métriques

Consultations de la notice

178

Téléchargements de fichiers

31