Clinical trial NCT05232071: 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
Official title: 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 Non-alcoholic Steatohepatitis (NASH) and Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NASH - Nonalcoholic Steatohepatitis
Diabetes Mellitus, Type 2
Lead sponsor: Inventiva Pharma
Sponsor class: INDUSTRY
First posted: 2022-02-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Male or female, aged ≥ 18 years at the time of signing informed consent
2. 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
3. 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
4. Negative pregnancy test at Screening for females of childbearing potential or at least two-year post-menopausal.

Exclusion Criteria:

Liver-related:

1. Documented causes of chronic liver disease other than NASH
2. Histologically documented liver cirrhosis (fibrosis stage F4)
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)
7. 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) )
8. Hemoglobin \< 110 g/L (11 g/dL) for females and \< 120 g/L (12 g/dL) for males
9. 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. 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
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 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 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:
20. BMI\>45 kg/m2 at screening
21. 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:

21. History of or current unstable cardiac dysrhythmias 22. Unstable heart failure 23. Uncontrolled hypertension 24. Stroke or transient ischemic attack

General safety:

25. 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.

Primary outcomes:
measure: 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
timeFrame: Date of randomisation until the end of treatment at week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Birmingham Digestive Health Research
state: Alabama
city: Chandler
country: United States
facility: Institute for Liver Health dba Arizona Liver Health
state: Arizona
city: Conway
country: United States
facility: ARcare Center for Clinical Research
state: Arkansas
city: Little Rock
country: United States
facility: ARcare Center for Clinical Research
state: Arkansas
city: Fountain Valley
country: United States
facility: Cure Clinical Research, LLC
state: California
city: Gardena
country: United States
facility: Velocity Clinical Research
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Poway
country: United States
facility: Cadena Care Institute, LLC
state: California
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Lehigh Acres
country: United States
facility: Galenus Group
state: Florida
city: Miami
country: United States
facility: Prolive Medical Research
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: South Bend
country: United States
facility: Digestive Health Research of Southern California
state: Indiana
city: Marrero
country: United States
facility: Tandem Clinical Research - New Orleans Area Site
state: Louisiana
city: Boston
country: United States
facility: Harvard Medical School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Florham Park
country: United States
facility: AIG Digestive Disease Research
state: New Jersey
city: Hermitage
country: United States
facility: Digestive Health Research
state: Tennessee
city: Austin
country: United States
facility: Accelemed Research Institute
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: Waco
country: United States
facility: Impact Research Institute
state: Texas
city: Wichita Falls
country: United States
facility: Digestive Health Research of North Texas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Central Virginia VA Healthcare System
state: Virginia
city: Brussels
country: Belgium
facility: CUB Erasme Hospital
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: UZ GENT
city: Angers
country: France
facility: CHU Angers_Service d'hepatogastro-enterologie
city: Limoges
country: France
facility: CHU Limoges
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pessac
country: France
facility: CHU Bordeaux
city: Toulouse
country: France
facility: Chu Rangueil
city: Vandoeuvre-lès-Nancy
country: France
facility: HGE CHRU Nancy
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St Georges Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
References: