The following is a summary of “An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis,” published in the July 2023 issue of the Pediatric Gastroenterology and Nutrition by Goyal et al.

Nonalcoholic hepatic steatosis is the prevailing chronic hepatopathy observed in pediatric patients. Elafibranor, a dual peroxisome proliferator-activated receptor α/δ agonist, has been suggested as a therapeutic option for nonalcoholic steatohepatitis (NASH). The objectives were to elucidate the pharmacokinetics (PK), safety, and tolerability of oral elafibranor at two doses (80 and 120 mg) in pediatric patients aged 8–17 years and evaluate alterations in aminotransferase levels. Pediatric patients diagnosed with nonalcoholic steatohepatitis (NASH) were randomly assigned to receive either open-label elafibranor at a daily dosage of 80 mg or 120 mg for 12 weeks. The intent-to-treat analysis comprised all participants who were administered at least one dose. 

The medical team conducted standard descriptive statistics and pharmacokinetic studies. A total of ten male individuals [with a mean age of 15.1 years and a standard deviation (SD) of 2.2] diagnosed with non-alcoholic steatohepatitis (NASH) were randomly assigned to receive either 80 mg (n = 5) or 120 mg (n = 5) of medication. The baseline average alanine aminotransferase (ALT) level was 82 U/L (standard deviation 13) and 87 U/L (standard deviation 20) for the 80 mg and 120 mg groups, respectively. Elafibranor exhibited rapid absorption and was well tolerated. The plasma exposure of Elafibranor demonstrated an increase between the 80 mg and 120 mg dosage, with a 1.9- and 1.3-fold increase in median maximum concentration (C_max) and area under the curve from 0 to 24 hours (AUC_0-24), respectively. 

The conclusion of the medical intervention resulted in an alanine aminotransferase (ALT) level of 52 U/L (standard deviation [SD] 20) for the group receiving a dosage of 120 mg. This was accompanied by a relative mean decrease in ALT from the initial measurement of -37.4% (SD 23.8%) after 12 weeks. The administration of elafibranor daily was well tolerated in pediatric patients diagnosed with nonalcoholic steatohepatitis (NASH). There was a 37.4% relative reduction from the mean baseline alanine aminotransferase (ALT) level in the 120 mg group. The removal of alanine aminotransferase (ALT) levels may be correlated with positive changes in liver tissue structure, making it a potential indicator of histological improvement in early-stage clinical studies. These findings may warrant additional investigation of elafibranor in pediatric patients with nonalcoholic steatohepatitis (NASH).

Source: journals.lww.com/jpgn/Abstract/2023/08000/An_Open_Label,_Randomized,_Multicenter_Study_of.5.aspx