A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and... | NCT04849728 | Trialant

A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and... | NCT04849728 | Trialant

Official Title: A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis Stages F2 and F3
Brief Summary: This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3
Detailed Description: Primary objectives

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives:

Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology.

Part B To assess the safety of lanifibranor beyond the DBPC period. 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 on other key histological features of NASH (only for DBPC period)

To assess the effect of lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period)

To assess the effect of lanifibranor on liver tests

To assess the effect of lanifibranor on glycaemic parameters

To assess the effect of lanifibranor on lipid parameters

To assess the effect of lanifibranor on liver stiffness and steatosis assessed by elastography.

To assess the effect of lanifibranor on health-related quality of life

To assess the safety of lanifibranor

To assess population PK modeling through plasma levels of lanifibranor using sparse sampling scheme (only for DBPC period)

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: Prescreening Criteria:

Diagnosed with NASH on prior liver biopsy

Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound

At least 3 of the components of metabolic syndrome

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

No qualitative change in 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): for at least 3 months

Vitamin E (if at a dose ≥400 IU/day): for at least 6 months

Statins: for at least 3 months

No qualitative change in dose for all other chronically administered drugs 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

AST<0.6 ULN if the liver biopsy has to be performed in the scope of the study

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

Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.

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)