Placebo-controlled, Proof-of-concept Study to Evaluate the Safety and Efficacy of Lanifibranor Alone and in Combination With SGLT2 Inhibitor EmpaGliflozin in patiEnts With NASH and Type 2 Diabetes Mellitus (LEGEND)
NASH - Nonalcoholic Steatohepatitis, Diabetes Mellitus, Type 2
About this trial
This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis
Eligibility Criteria
Inclusion Criteria:
- Male or female, aged ≥ 18 years at the time of signing informed consent
- Diagnosis of NASH, based on histology or ct1>875msecs by LiverMuliScan at screening
- HbA1c at screening ≥ 7.0 and ≤ 10.0%, on diet alone, or on metformin and/or dipeptidyl peptidase 4 inhibitor (DPP-IVi) therapy. Both with doses to be stable for 3 months
- Negative pregnancy test at Screening for females of childbearing potential or at least two-year post-menopausal.
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
- Documented history of human immunodeficiency virus (HIV) infection
- ALT or AST > 5 × upper limit of normal (ULN)
Abnormal liver function as defined by central laboratory evaluation:
Albumin < LLN INR ≥ 1.3 (unless patient is on anticoagulants)
Total bilirubin level ≥ 1.3 mg/dL (22.2 µmol/L) (patients with a documented history of Gilbert's syndrome can be enrolled if direct bilirubin is within normal reference range)
- Hemoglobin < 110 g/L (11 g/dL) for females and < 120 g/L (12 g/dL) for males
- WBC < LLN
- Platelet count < 150,000/µL
- ALP > 2 × ULN
- Patient currently receiving any approved treatment for NASH or obesity
- Current or recent history (< 5 years) of significant alcohol consumption
Administration of drugs known to produce hepatic steatosis in the 6 months prior to Screening.
Diabetes related:
- Diabetes mellitus other than type 2
- Diabetic ketoacidosis at Screening
- Current treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA), insulin or sulfonylurea or treatment within the last 3 months prior to Screening
Patients on pioglitazone in the last 12 months prior to Screening. Patients on metformin, DPP-IVi, thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels, unless on stable doses in last 3 months
Obesity related:
- BMI>45 kg/m2 at screening
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.
Cardiovascular related:
- History of or current unstable cardiac dysrhythmias
- Unstable heart failure
- Uncontrolled hypertension
Stroke or transient ischemic attack
General safety:
- Significant systemic or major illnesses other than liver disease and pulmonary disease, organ transplantation, serious psychiatric disease, that, in the opinion of the investigator, would preclude treatment with lanifibranor and/or adequate follow up
- Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value < 60 mL/min
- Concomitant treatment with PPAR-⍺ agonists (fibrates)
- Have a known hypersensitivity to any of the IMPs
- Previous exposure to lanifibranor or empagliflozin
- Present pregnancy/lactation
- Metallic implant of any sort that prevents MRI examination
- Participation in any clinical trial of an approved or non approved investigational medicinal product/device within 3 months from Screening or five half-lives of the investigational drug from Screening.
Sites / Locations
- Birmingham Digestive Health ResearchRecruiting
- Institute for Liver Health dba Arizona Liver HealthRecruiting
- Institute for Liver Health dba Arizona Liver HealthRecruiting
- ARcare Center for Clinical ResearchRecruiting
- ARcare Center for Clinical ResearchRecruiting
- Cure Clinical Research, LLCRecruiting
- Velocity Clinical ResearchRecruiting
- National Research InstituteRecruiting
- Cadena Care Institute, LLCRecruiting
- Florida Research InstituteRecruiting
- Galenus GroupRecruiting
- Prolive Medical ResearchRecruiting
- Indiana University School of MedicineRecruiting
- Digestive Health Research of Southern CaliforniaRecruiting
- Tandem Clinical Research - New Orleans Area SiteRecruiting
- Harvard Medical SchoolRecruiting
- Mayo ClinicRecruiting
- AIG Digestive Disease ResearchRecruiting
- Digestive Disease Research Center, LLCRecruiting
- Digestive Health ResearchRecruiting
- Accelemed Research InstituteRecruiting
- Dallas Diabetes Research CenterRecruiting
- American Research CorporationRecruiting
- Diabetes & Glandular Disease Clinic, P.A.Recruiting
- Impact Research InstituteRecruiting
- Digestive Health Research of North TexasRecruiting
- University of VirginiaRecruiting
- Central Virginia VA Healthcare SystemRecruiting
- CUB Erasme HospitalRecruiting
- Cliniques Universitaires Saint-LucRecruiting
- Universitair Ziekenhuis AntwerpenRecruiting
- AZ Maria MiddelaresRecruiting
- UZ GENTRecruiting
- CHU Angers_Service d'hepatogastro-enterologieRecruiting
- CHU LimogesRecruiting
- Hopital Saint AntoineRecruiting
- CHU BordeauxRecruiting
- Chu RangueilRecruiting
- HGE CHRU NancyRecruiting
- Amsterdam UMCRecruiting
- Hull University Teaching Hospital
- King's College HospitalRecruiting
- St Georges Hospital
- Royal Victoria InfirmaryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
Lanifibranor (IVA337) (800 mg/day)
Matching placebo
Lanifibranor (IVA337) (800 mg/day) plus Empagliflozin (10mg/day)
2 Lanifibranor tablets 400 mg with food --> once a day (quaque die, QD)
2 Placebo to match tablets with food --> once a day (quaque die, QD)
2 Lanifibranor tablets 400 mg plus 1 Empagliflozin tablet 10mg with food --> once a day (quaque die, QD)