Background Non-
alcoholic steatohepatitis (NASH), a multifactorial disease, can progress to hepatic
fibrosis and
cirrhosis. The Peroxysomal Proliferator-Activated Receptors, PPARα, β/δ and γ, play a central role in the regulation of
glucose and lipid metabolism and of the inflammatory and fibrogenic pathways in liver and in other organs that all contribute to NASH pathogenesis.
Lanifibranor (
IVA337), a panPPAR agonist, by acting on these three different
PPAR isotypes, combines pharmacological effects that could address the different components of the disease as demonstrated in preclinical models. Objectives NATIVE study (EudraCT: 2016-001979-70, NCT: NCT03008070) aims to assess the safety and the efficacy of a 24-week treatment with
lanifibranor (800 and 1200 mg/day) in adult non-cirrhotic NASH patients. The primary efficacy endpoint is a 2-point reduction in the activity part of the Steatosis Activity
Fibrosis (
SAF) histological score (combining
inflammation and ballooning) without worsening of
fibrosis. Design NATIVE is a Phase 2b randomised, placebo-controlled, double-blind, parallel-assignment, dose-range study. Eligible adult patients with a confirmed histological diagnosis of NASH should have a
SAF Activity score of 3 or 4 (>2) and a
SAF Steatosis score ≥ 1. There is no specific criterion related to the
fibrosis score except that patients with
cirrhosis (F4) were excluded. Summary This study will evaluate the efficacy of a 24-week treatment of NASH with
lanifibranor based on histological evaluations (
SAF score) by biopsy. The number of responders according to the
SAF Activity score-based definition from baseline to 24 weeks will be compared between groups and serves as primary endpoint.