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 2 (F2)/fibrosis 3 (F3) stage of liver fibrosis

Phase 3

Recruiting

• Conditions: Liver disease; 10019654

• Registration Number: NL-OMON56041
• Lead Sponsor: Inventiva S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 25

Inclusion Criteria

To be eligible to be screened for the study, potential patients must meet one
of the following criteria (See Section 13.5):
1. Diagnosed with NASH on prior liver biopsy by local pathology reading
excluding those read as F4 fibrosis (can have been any time in past for this
qualification purpose)
2. Type 2 diabetes with high waist circumference or obesity, or hepatic
steatosis on ultrasound
3. At least three of the following components of metabolic syndrome:
o High waist circumference or obesity, or hepatic steatosis on ultrasound
o Type 2 diabetes
o Low HDL cholesterol
o High triglyceride level
o Arterial hypertension

For randomisation of an eligible patient, all inclusion criteria must be
answered *yes* at the time of Screening and re-confirmed at Baseline (i.e.,
before randomisation), except for laboratory tests for which Screening results
are used for randomisation. If information is not able to be confirmed in the
medical record, responses will be obtained in a patient interview:
1. Able to understand the nature of the study, willing and able to comply with
the study procedures and restrictions, and able to provide signed, dated and
written informed consent obtained before any study-related activities, sampling
and analysis.
2. The patient will be willing to continue on the study in case of moving or
relocation during the first 72 weeks of the study.
3. Male or female, aged >=18 years at the time of signing informed consent
4. If biopsy is performed before Screening, i.e. if a historical biopsy is
available, a histological diagnosis of NASH with liver fibrosis must be made no
more than >7 months before randomisation.
5. Main cohort: Upon central biopsy reading process: diagnosis of NASH
according to the Steatosis-Activity-Fibrosis (SAF):
a) Steatosis score >=1
b) Activity score: A3 or A4
c) Fibrosis score: F2 or F3
This SAF-based diagnosis translates into the following CRN NAS-based diagnosis:
• CRN-Steatosis score >=1, CRN-Inflammation (CRN-I) score >=1 and CRN-Ballooning
(CRN-B) score >=1
• NAS score >=5, or [NAS score >=4 with either CRN-I >=2 or CRN-B >=2]
• CRN-Fibrosis score: F2 or F3

Exploratory cohort: Patients who, upon central biopsy reading process, do not
meet the eligibility criteria described above but fulfil the following
criteria: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
a) Steatosis score >=1
b) Activity score >=2 with SAF-Inflammation score >=1 and SAF-Ballooning score >=1
c) Fibrosis score: any stage (F1 to F4)

6. MELD score <=12 (unless patient is on anticoagulants)
7. For patients receiving the concomitant medications listed below: no
qualitative change in dose are allowed (changes having minimal clinical impact
like temporary cessation/change between class of drugs are allowed), for the
specified period prior to the qualifying liver biopsy and dose must remain
stable from the time of the liver biopsy until the Baseline visit (Visit 0):
a) Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1
receptor agonists including combinations) or sodium-glucose co transporter-2
inhibitors (SGLT2 inhibitors): for at least 3 months
b) Vitamin E (if at a dose >=400 IU/day): for at least 6 months
c) Statins: for at least 3 months
d) Anti-obesity tre

Exclusion Criteria

For randomisation of an eligible patient, all the following exclusion criteria
must be answered *no* at Screening and re-confirmed at Baseline (i.e. before
randomisation), except for laboratory tests for which Screening results are
used for randomisation:
Liver-related:
1. Documented causes of chronic liver disease other than NASH including, but
not restricted to:
a) Viral hepatitis documented with
i. Positive hepatitis B surface antigen (HBsAg)
ii. Positive hepatitis C virus ribonucleic acid (RNA) (tested for in case of
known cured hepatitis C virus [HCV] infection or positive HCV serology at
Screening). Patients with a history of HCV infection can be included if HCV PCR
is negative since more than 3 years.
b) Drug-induced liver disease
c) Alcoholic liver disease: patients with a history of alcohol use who present
an AST:ALT ratio of >=2 and gamma-glutamyltransferase (GGT) >2 × upper limit of
normal (ULN) and macrocytosis with mean corpuscular volume (MCV) >95 fL without
known aetiology of Vitamin B12 insufficiency
d) Autoimmune hepatitis (see Exclusion criteria 44 for more information)
e) Wilson*s disease
f) Haemochromatosis
g) Primary biliary cholangitis
h) Primary sclerosing cholangitis
i) Alpha-1-antitrypsin deficiency
j) Chronic portal vein thrombosis or splenic vein thrombosis
2. Histologically documented liver cirrhosis in the most recent historical
biopsy (fibrosis stage F4) or suspicion at Screening of cirrhosis based on
clinic biochemical and imaging criteria upon investigator*s assessment (see
Section 9.1.1)
3. History or current diagnosis of hepatocellular carcinoma (HCC)
4. History of or planned liver transplant
5. Inability or unwillingness to undergo a liver biopsy at Screening (if a
suitable historical biopsy is unavailable for central review) and at Week 72
6. Positive human immunodeficiency virus (HIV) serology
7. ALT or AST >5 × ULN
7.1. AST < 0.60 × ULN if the screening liver biopsy has to be performed in the
scope of the study
7.2. Liver Stiffness Measurement (LSM) < 6 kPa by transient elastography (or
equivalent) during screening if the screening liver biopsy has to be performed
in the scope of the study.
8. Abnormal synthetic liver function of any of the following:
a) Albumin below the lower limit of the normal range
b) International normalised ratio (INR) >=1.3 (unless patient is on
anticoagulants)
c) Total bilirubin level >=1.5 mg/dL (25.6 µmol/L). Patients with a history of
Gilbert*s syndrome can be enrolled if the direct bilirubin is <=0.45 mg/dL (7.7
µmol/L)
9. Haemoglobin < 110 g/L (11g/dL) for females and <120 g/L (12g/dL) for males
10. Leucocytes count < LLN. A lower count is acceptable in patients with benign
ethnic neutropenia, if considered to be clinical insignificant by the
investigator.
11. Platelet count <140,000/µL
12. Alkaline phosphatase (ALP) >2 × ULN
13. Patient currently receiving any approved treatment for NASH
14. Current or recent history (<5 years) of significant alcohol consumption,
which is typically defined as higher than 30 g pure alcohol per day for men and
as higher than 20 g pure alcohol per day for women (please also refer to
Section 13.1). No binge drinking during the last year. Consuming 75 g pure
alcohol (male), or 60 g pure alcohol (female), or more in about 2 hours
15.

Study & Design

• Study Type: Interventional
• Study Design: Not specified