A placebo-controlled, proof-of-concept study to evaluate the safety and efficacy of Lanifibranor alone and in combination with the sodium-glucose transport protein 2 (SGLT2) inhibitor EmpaGliflozin in patiEnts with Nonalcoholic steatohepatitis (NASH) and type 2 Diabetes mellitus (T2DM)
- Conditions
- Diabetes type 2diabetesNon-alcoholic Steatohepatitisliver inflammation1001965410018424
- Registration Number
- NL-OMON53417
- Lead Sponsor
- Inventiva S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
1. Able to understand the nature of the study, willing and able to comply with
the study procedures and restrictions, and willing to provide informed consent
obtained before any study-related activities
2. The patient is willing to continue on the study in case of moving or
relocating to a different region/city where there would be no active study site
3. Able to communicate meaningfully with the Investigator and legally competent
to provide written informed consent
4. Male or female, aged >= 18 years at the time of signing informed consent
5. Diagnosis of NASH
a. based on a historical (within 12 months prior to Screening) liver biopsy
with a non alcoholic fatty liver disease activity score (NAS) >= 4 with a score
of one or more in each sub-component (steatosis, hepatocyte ballooning, lobular
inflammation) and no documented cirrhosis in the last 12 months prior to
Screening OR
b. NASH screening:
i. High Risk NASH defined as cT1 >=> 875 ms assessed by LiverMultiScan® OR
ii. NASH defined as cT1 >= 825 ms assessed by LiverMultiScan® and hepatic fat
content >= 10% assessed by MRI-PDFF
6. HbA1c at screening >= 7.0 and <= 10.0%, on diet alone, or on metformin (>=
1,000 mg/day), and/or dipeptidyl peptidase 4 inhibitor (DPP-IVi) therapy. Doses
have no qualitative change for 3 months prior to informed consent. These
medicines will be continued at stable doses during the entire study.
7. Negative pregnancy test at Screening for females of childbearing potential
or at least two-year post-menopausal. Women of childbearing potential (i.e.,
fertile, following menarche and until becoming post-menopausal unless
permanently sterile) have to use a highly effective method of contraception
throughout the study and for one month after treatment discontinuation. Highly
effective contraceptive methods are defined as follows: combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition of
ovulation (oral, intravaginal, transdermal), progestogen-only hormonal
contraception associated with inhibition of ovulation (oral, injectable,
implantable), intrauterine device (IUD), intrauterine hormone-releasing system
(IUS), bilateral tubal occlusion, vasectomized partner (provided he is her sole
sexual partner and he has received medical assessment of the surgical success),
and true sexual abstinence (when this is in line with the preferred and usual
lifestyle of the patient) whereas periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
Liver-related:
1. Documented causes of chronic liver disease other than NASH (see protocol for
details, see exclusion criteria no 50 for autoimmune diseases)
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. Autoimmune hepatitis
d. Wilson*s disease
e. Hemochromatosis
f. Primary biliary cholangitis
g. Primary sclerosing cholangitis
h. *1-antitrypsin deficiency
2. Histologically documented liver cirrhosis (fibrosis stage F4), based on a
historical biopsy (within 12 months prior to Screening); or diagnosis of
cirrhosis at Screening based on clinic biochemical and imaging criteria
(FibroScan® value confirmed >= 14 kPa and FIB-4 > 3.25 provided to the site by
the central lab)
3. History or current diagnosis of hepatocellular carcinoma (HCC)
4. History of or planned liver transplant
5. Documented history of human immunodeficiency virus (HIV) infection
6. ALT or AST > 5 × upper limit of normal (ULN) at Screening
7. Abnormal liver function as defined by central laboratory evaluation of any
of the following:
a. Albumin < lower limit of normal range (LLN)
b. International normalized ratio (INR) >= 1.3 (unless patient is on
anticoagulants)
c. Total bilirubin level >= 1.5 mg/dL (25.7 µmol/L) (Patients with a documented
history of Gilbert*s syndrome can be enrolled if direct bilirubin is <= 0.45
mg/dL (7.7µmol/L))
8. Hemoglobin < 110 g/L (11 g/dL) for females and < 120 g/L (12 g/dL) for males
9. White blood cell count (WBC) < LLN. A lower count is acceptable in patients
with benign ethnic neutropenia, if considered to be clinical insignificant by
the investigator.
10. Platelet count < 140,000/µL
11. Alkaline phosphatase (ALP) > 2 × ULN
12. Patient currently receiving any approved treatment for NASH or obesity
13. 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
14. Administration of drugs known to produce hepatic steatosis in the 6 months
prior to Screening (such as high-dose estrogens, methotrexate, tetracycline, or
amiodarone) (see also Section 13.2)
Diabetes related:
15. Diabetes mellitus other than type 2 (e.g., type 1, endocrinopathy, and
genetic syndromes)
16. Diabetic ketoacidosis at Screening
17. Current treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA),
insulin or sulfonylurea or treatment within the last 3 months prior to Screening
18. Patients on pioglitazone in the last 12 months prior to Screening
19. Patients on any of the following medications unless the patient had no
qualitative change in doses of such agents for the past 3 months before
Screening: metformin, DPP-IVi, thiazide or furosemide diuretics, beta-blockers,
or other chronic medications with known adverse ef
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint of this study is the absolute change in HbA1c<br /><br>from baseline<br /><br>(Week 0) to Week 24. </p><br>
- Secondary Outcome Measures
Name Time Method