From the Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, UC San Diego, School of Medicine, La Jolla, CA.
the Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, CA.
J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):160-165. doi: 10.1097/MPG.0000000000003796. Epub 2023 Apr 21.
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 nonalcoholic steatohepatitis (NASH). The aims were to (1) describe pharmacokinetics (PK), safety, and tolerability of oral elafibranor at 2 doses (80 and 120 mg) in children 8-17 years and (2) assess changes in aminotransferases.
Children with NASH were randomized to open-label elafibranor 80 mg or 120 mg daily for 12 weeks. The intent-to-treat analysis included all participants who received at least 1 dose. Standard descriptive statistics and PK analyses were performed.
Ten males [mean 15.1 years, standard deviation (SD) 2.2] with NASH were randomized to 80 mg (n = 5) or 120 mg (n = 5). Baseline mean alanine aminotransferase (ALT) was 82 U/L (SD 13) and 87 U/L (SD 20) for 80 mg and 120 mg groups, respectively. Elafibranor was rapidly absorbed and well tolerated. Elafibranor plasma exposure increased between the 80 mg and 120 mg dose with a 1.9- and 1.3-fold increase in median Cmax and AUC 0-24 , respectively. End of treatment mean ALT was 52 U/L (SD 20) for the 120 mg group, with a relative mean ALT change from baseline of -37.4% (SD 23.8%) at 12 weeks.
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 120 mg 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.
非酒精性脂肪性肝病是儿童中最常见的慢性肝病。过氧化物酶体增殖物激活受体α/δ双重激动剂 Elafibranor 已被提议用于治疗非酒精性脂肪性肝炎（NASH）。目的是：（1）描述 8-17 岁儿童口服 Elafibranor 2 个剂量（80 和 120mg）的药代动力学（PK）、安全性和耐受性；（2）评估氨基转移酶的变化。
患有 NASH 的儿童随机分为 Elafibranor 每日 80mg 或 120mg 开放标签治疗 12 周。意向治疗分析纳入了至少接受 1 次治疗的所有参与者。采用标准描述性统计和 PK 分析。
10 名男性（平均年龄 15.1 岁，标准差 2.2）患有 NASH，随机分为 80mg（n=5）或 120mg（n=5）组。80mg 和 120mg 组的基线平均丙氨酸氨基转移酶（ALT）分别为 82U/L（SD 13）和 87U/L（SD 20）。Elafibranor 吸收迅速，耐受性良好。Elafibranor 血浆暴露量随 80mg 和 120mg 剂量增加，Cmax 和 AUC0-24 的中位数分别增加 1.9 倍和 1.3 倍。120mg 组治疗结束时的平均 ALT 为 52U/L（SD 20），12 周时的平均 ALT 相对变化为-37.4%（SD 23.8%）。
NASH 儿童每日口服 Elafibranor 耐受性良好。120mg 组的平均基线 ALT 相对降低 37.4%。ALT 的降低可能与肝组织学的改善相关，因此可被视为早期临床试验中组织学的替代指标。这些结果可能支持进一步研究 Elafibranor 在 NASH 儿童中的应用。
