A Phase 3 Study Evaluating Long-term Efficacy and Safety of Lanifibranor in Adult Patients With (NASH) and Fibrosis 2 (F2)/Fibrosis 3 (F3) Stage of Liver Fibrosis (NATiV3)
- Study HIC#:2000030905
- Last Updated:11/05/2023
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage 2 or 3.
- Age18 years and older
- GenderBoth
Contact Us
For more information about this study, including how to volunteer, contact:
Elizabeth Szymanski
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Trial Purpose and Description
Primary objectives
This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage 2 or 3 and consists of 2 parts - Part 1 and Part 2, with the following primary objectives:
Part 1 To assess the effect of lanifibranor compared to placebo on NASH resolution and improvement of fibrosis assessed by liver histology.
Part 2 To assess the effect of lanifibranor compared to placebo on delaying NASH disease progression measured by a composite endpoint that includes progression to cirrhosis, liver-related clinical outcome events, or all-cause death.
Secondary objectives
Key secondary objectives of Part 1:
- To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis
- To assess the effect of lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH
Other secondary objectives of both Part 1 and Part 2:
- To assess the effect of lanifibranor compared to placebo on other key histological features of NASH
- To assess the effect of lanifibranor compared to placebo on NASH resolution and improvement of fibrosis in diabetic patients
- To assess the effect of lanifibranor compared to placebo on liver function tests
- To assess the effect of lanifibranor compared to placebo on glycaemic parameters
- To assess the effect of lanifibranor compared to placebo on lipid parameters
- To assess the effect of lanifibranor compared to placebo on liver stiffness
- To assess the effect of lanifibranor compared to placebo on health-related quality of life
- To assess the long-term safety (up to 7 years) of lanifibranor
- To assess population PK modeling of lanifibranor using sparse sampling scheme
Eligibility Criteria
Inclusion Criteria:
- Male or female, aged ≥18 years at the time of signing informed consent
- Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
- Steatosis score ≥1
- Activity score: A3 or A4
- Fibrosis score: F2 or F3
- Stable dose for the drugs listed below:
- Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): Stable dose for at least 3 months
- Vitamin E (if at a dose ≥400 IU/day): Stable dose for at least 6 months
- Statins: Stable dose for at least 3 months
- All other chronically administered drugs must be stable for at least 3 months prior to Screening
- Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
- Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.
Exclusion Criteria:
Liver-related:
- Documented causes of chronic liver disease other than NASH
- Histologically documented liver cirrhosis (fibrosis stage F4)
- History or current diagnosis of hepatocellular carcinoma HCC
- History of or planned liver transplant
- Positive human immunodeficiency virus (HIV) serology
- ALT or AST >5 × ULN
- Abnormal synthetic liver function as defined by Screening central laboratory evaluation
- Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males
- Patient currently receiving any approved treatment for NASH or obesity
- Current or recent history (<5 years) of significant alcohol consumption
- Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy
Glycaemia related:
- HbA1c >9% at Screening
- Diabetes mellitus other than type 2
- Current treatment with insulin
- Previous or current treatment with PPAR-gamma agonists (thiazolidinediones [TZDs])
Obesity related:
- Bariatric surgery: Restrictive procedures are allowed, if performed >6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.
Cardiovascular related:
- History of heart failure with reduced left ventricular ejection fraction (LVEF)
- Atrial fibrillation requiring anticoagulation
- Unstable heart failure
- Uncontrolled hypertension at Screening (values >160/100 mm Hg)
General safety:
- Women currently breastfeeding
- Previous exposure to lanifibranor
- Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
- Concomitant treatment with PPAR-alpha agonists (fibrates)