A clinical study to find out how safe and effective Lanifibranor is in patientswith Non-alcoholic steatohepatitis (NASH) and type 2 Diabetes.Lanifibranor will be studied when taken alone or in combination withEmpagliflozin.

Phase 1

• Conditions: Type 2 Diabetes (T2DM) with Non-Alcoholic Steatohepatitis (NASH); MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2021-005057-87-NL
• Lead Sponsor: Inventiva S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-15
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

For an eligible patient, all inclusion criteria must be answered yes” at Screening and re-confirmed at the time of randomization procedure and at Baseline (i.e., before treatment initiation). Laboratory tests taken during the screening period will be used to determine eligibility. If information cannot 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 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 at Screening
b1. High Risk NASH defined as cT1 = 875 ms assessed by LiverMultiScan® OR
b2. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 47
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

A.Liver-related:
1. Documented causes of chronic liver disease other than NASH (see protocol for details, see exclusion criteria no 50 for autoimmune hepatitis)
2. Histologically documented liver cirrhosis (fibrosis F4); or diagnosis ofcirrhosis at Screening
3. History or current diagnosis of hepatocellular carcinoma (HCC)
4. History of or planned liver transplant
5. Documented history of HIV infection
6. ALT or AST > 5 × upper limit of normal (ULN) at Screening
7. Abnormal liver function as any :
a. Albumin < lower limit of normal range (LLN)
b. INR = 1.3 (unless patient is on anticoagulants)
c. Total bilirubin level = 1.5 mg/dL (25.7 µmol/L). Patients with Gilbert's syndrome can be enrolled if direct bilirubin is = 0.45 mg/dL (7.7 µmol/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 < LLN or a lower count in patients with benignethnic 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. No binge drinking during the last year.
14. Administration of drugs known to produce hepatic steatosis in the 6 months prior to Screening
B. Diabetes related (see protocol/synopsis for details)

C. Obesity related (see protocol/synopsis for details)
20. BMI > 45 kg/m2 at Screening
21. Weight change > 5% in 3 months prior to Screening
22. Introduction of anti-obesity drug or restrictive bariatric surgery in past 12 months prior to Screening or planned bariatric surgery throughWeek 24
23. Participation in an organized weight loss program in past 6 months prior to Screening or planned participation through Week 24

D. Cardiovascular related (see protocol/synopsis for details)

E. General safety:
30.Significant systemic or major illnesses other than liver disease that would preclude treatment with lanifibranor and/or empagliflozin
31.Any condition which might jeopardize a patient’s safety or compliance with the protocol, or warrants exclusion from the study
32.Cancer: Presenceor history of malignancy within 5 years prior to Screening and/or active neoplasm at Screening.
33.History of bladder disease and/or persistent hematuria within 6 months prior to Screening or current hematuria unless due to a urinary tract infection
34.Renal impairment measured as eGFR < 60 mL/min as determined by MDRD
35.Total creatine kinase > 1.5 x ULN
36.History of pancreatitis, or confirmed pancreatic lipase > 1.3 x ULN, or > 2.0 x ULN upon repeated test within 3 weeks if on a DPP-IVi
37.Concomitant treatment with PPAR-? agonists (fibrates);
38.Patients on Vitamin E at doses = 400 IU/day; unless no qualitative change in dose
39.SARS-CoV-2 infections requiring hospitalization in the last 3 months or current SARS-CoV-2 infection confirmed by a validated test.
40.Major surgery scheduled during the study
41.Hypersensitivity to any of the ingredients of the IMPs
42.Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
43.Previous exposure to lanifibranor or empagliflozin
44.Osteopenia, or any otherbone disease.
45.Claustrophobia that prevents tolerance of MRI scanning procedure.
46.Metallic implant that prevents MRI examination or an

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified