A clinical study to evaluate the safety and efficacy of lanifibranor alone and in combination with the sodium-glucose transport protein 2 (SGLT2) inhibitor empaGliflozin in adult patients with non-alcoholic steatohepatitis (NASH) and type 2 Diabetes mellitus (T2DM)

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-FR
• Lead Sponsor: Inventiva S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-04
• 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 Baseline (i.e., before randomization). 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.high-risk NASH defined as cT1 > 875 ms assessed by LiverMultiScan® at Screening
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 to be stable 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 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

Liver-related:
1.Documented causes of chronic liver disease other than NASH
2.Histologically documented liver cirrhosis (fibrosis stage F4); or diagnosis of cirrhosis at Screening
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 = 1.3 mg/dL (22.2 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 (WBC) < LLN
10.Platelet count < 150,000/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

Diabetes related:
15.Diabetes mellitus other than type 2
16.Diabetic ketoacidosis at Screening
17.Current treatment with 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 has been on stable 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 effects on glucose tolerance levels. Patients taking systemic glucocorticoids will be excluded.
Obesity related:
20.BM) > 45 kg/m2 at Screening
21.Weight change > 5% in the 3 months prior to Screening
22.Introduction of an anti-obesity drug or restrictive bariatric surgery in the past 12 months prior to Screening or planned bariatric surgery through Week 24
23.Participation in an organized weight loss program in the past 6 months prior to Screening or planned participation through Week 24
Cardiovascular related:
24.History of (within 3 months prior to Screening) or current unstable cardiac dysrhythmias
25.NT-proBNP > 900 pg/mL
26.Unstable heart failure
27.Any other clinically significant cardiovascular event requiring hospitalization within 6 months before Screening
28.Uncontrolled hypertension at Screening (systolic blood pressure [SBP] > 160 mmHg and/or diastolic blood pressure [DBP] > 100 mmHg
29.Stroke or transient ischemic attack within 6 months prior to Screening
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: Presence or 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

Study & Design

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