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
- Conditions
- Diabetes Mellitus, Type 2NASH - Nonalcoholic Steatohepatitis
- Interventions
- Registration Number
- NCT05232071
- Lead Sponsor
- Inventiva Pharma
- Brief Summary
The study in the T2DM population is intended to confirm the lanifibranor effect versus placebo on glycemic control and assess a positive effect of the combination of lanifibranor with an SGLT2 inhibitor on glycemic control.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- Male or female, aged ≥ 18 years at the time of signing informed consent
- Diagnosis of NASH, based on histology or cT1≥875ms assessed by LiverMultiScan or cT1≥825ms assessed by LiverMultiScan and hepatic fat content ≥ 10% assessed by MRI-PDFF 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.
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 ≥ 1.5 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 (7.7 μmol/L) )
-
Hemoglobin < 110 g/L (11 g/dL) for females and < 120 g/L (12 g/dL) for males
-
WBC < LLN. A lower count is acceptable in patients with benign ethnic neutropenia, if considered to be clinical insignificant by the investigator
-
Platelet count < 140,000/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 22. Unstable heart failure 23. Uncontrolled hypertension 24. 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 26. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value < 60 mL/min 27. Concomitant treatment with PPAR-⍺ agonists (fibrates) 28. Patients on Vitamin E at doses ≥ 400 IU/day; doses of ≥ 400 IU/day are allowed when no qualitative change in dose for 6 months prior to Screening 29. Have a known hypersensitivity to any of the IMPs 30. Previous exposure to lanifibranor or empagliflozin 31. Present pregnancy/lactation 32. Metallic implant of any sort that prevents MRI examination 33. 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Matching placebo Placebo 2 Placebo to match tablets with food --\> once a day (quaque die, QD) Lanifibranor (IVA337) (800 mg/day) IVA337 2 Lanifibranor tablets 400 mg with food --\> once a day (quaque die, QD) Lanifibranor (IVA337) (800 mg/day) plus Empagliflozin (10mg/day) IVA337 2 Lanifibranor tablets 400 mg plus 1 Empagliflozin tablet 10mg with food --\> once a day (quaque die, QD) Lanifibranor (IVA337) (800 mg/day) plus Empagliflozin (10mg/day) Empagliflozin 2 Lanifibranor tablets 400 mg plus 1 Empagliflozin tablet 10mg with food --\> once a day (quaque die, QD)
- Primary Outcome Measures
Name Time Method Assessment of the effect of lanifibranor alone compared to placebo and the effect of lanifibranor in combination with empagliflozin compared to placebo on absolute change in HbA1c from baseline (Week 0) to Week 24 Date of randomisation until the end of treatment at week 24 Absolute change in HbA1c from baseline (Week 0) to Week 24
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (41)
Birmingham Digestive Health Research
🇺🇸Homewood, Alabama, United States
Institute for Liver Health dba Arizona Liver Health
🇺🇸Chandler, Arizona, United States
Cure Clinical Research, LLC
🇺🇸Fountain Valley, California, United States
Velocity Clinical Research
🇺🇸Gardena, California, United States
Cadena Care Institute, LLC
🇺🇸Poway, California, United States
National Research Institute
🇺🇸Huntington Park, California, United States
Galenus Group
🇺🇸Lehigh Acres, Florida, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Prolive Medical Research
🇺🇸Miami, Florida, United States
Digestive Health Research of Southern California
🇺🇸South Bend, Indiana, United States
Harvard Medical School
🇺🇸Boston, Massachusetts, United States
Tandem Clinical Research - New Orleans Area Site
🇺🇸Marrero, Louisiana, United States
Dallas Diabetes Research Center
🇺🇸Dallas, Texas, United States
Impact Research Institute
🇺🇸Waco, Texas, United States
Digestive Health Research of North Texas
🇺🇸Wichita Falls, Texas, United States
UZ GENT
🇧🇪Gent, Belgium
CHU Limoges
🇫🇷Limoges, France
CHU Angers_Service d'hepatogastro-enterologie
🇫🇷Angers, France
CHU Bordeaux
🇫🇷Pessac, France
Hopital Saint Antoine
🇫🇷Paris, France
Chu Rangueil
🇫🇷Toulouse, France
Hull University Teaching Hospital
🇬🇧Hull, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
St Georges Hospital
🇬🇧London, United Kingdom
CUB Erasme Hospital
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Digestive Health Research
🇺🇸Hermitage, Tennessee, United States
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
ARcare Center for Clinical Research
🇺🇸Little Rock, Arkansas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
AZ Maria Middelares
🇧🇪Gent, Belgium
AIG Digestive Disease Research
🇺🇸Florham Park, New Jersey, United States
HGE CHRU Nancy
🇫🇷Vandoeuvre-lès-Nancy, France
Accelemed Research Institute
🇺🇸Austin, Texas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
American Research Corporation
🇺🇸San Antonio, Texas, United States
Diabetes & Glandular Disease Clinic, P.A.
🇺🇸San Antonio, Texas, United States
Central Virginia VA Healthcare System
🇺🇸Richmond, Virginia, United States