https://pubmed.ncbi.nlm.nih.gov/37084342/ NAFLD

J Pediatr Gastroenterol Nutr. 2023 Apr 21.

doi: 10.1097/MPG.0000000000003796.Online ahead of print.

An Open Label, Randomized, Multicenter Study of Elafibranor in Children with Nonalcoholic Steatohepatitis

Nidhi P Goyal 1 2, Ali Mencin 3, Kimberly P Newton 1 2, Janis Durelle 1, Carissa Carrier 1, Patricia Ugalde-Nicalo 1, Benoit Noel 1, Julie Mouton 4, Dawn Vargas 1, David Magrez 4, Bachirou Tadde 4, Pascal Birman 4, Brookie M Best 5 6, Carol Addy 1, Jeffrey B Schwimmer 1 2

Abstract
Objectives: Nonalcoholic fatty liver disease is the most common chronic liver disease in children. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been proposed as a treatment for NASH. The aims were to: 1. describe pharmacokinetics, safety, and tolerability of oral elafibranor at 2 doses (80 and 120mg) in children 8-17 years and 2. assess changes in aminotransferases.

Methods: Children with NASH were randomized to open-label elafibranor 80mg or 120mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least one dose. Standard descriptive statistics and PK analyses were performed.

Results: Ten males (mean 15.1yrs, SD 2.2) with NASH were randomized to 80mg (n=5) or 120mg (n=5). Baseline mean ALT was 82 U/L (SD 13) and 87 U/L (SD 20) for 80mg and 120mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80mg and 120mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC0-24, respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.

Conclusions: Once daily dosing of elafibranor was well tolerated in children with NASH. There was a 37.4% relative reduction from mean baseline ALT in the 120mg group. Decreasing ALT may be associated with improvement in liver histology, thus could be considered a surrogate for histology in early phase trials. These results may support further exploration of elafibranor in children with NASH