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.