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

Diabetes Mellitus, Type 2 Clinical Trial

— LEGEND  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05232071
• Other study ID #: 337HNAS21016
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 29, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Inventiva Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: December 31, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Fatty Liver
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• IVA337
800 mg
• Placebo
Placebo to match
• Empagliflozin
10 mg

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	CUB Erasme Hospital	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	AZ Maria Middelares	Gent
Belgium	UZ GENT	Gent
France	CHU Angers_Service d'hepatogastro-enterologie	Angers
France	CHU Limoges	Limoges
France	Hopital Saint Antoine	Paris
France	CHU Bordeaux	Pessac
France	Chu Rangueil	Toulouse
France	HGE CHRU Nancy	Vandoeuvre-lès-Nancy
Netherlands	Amsterdam UMC	Amsterdam
United Kingdom	King's College Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United States	Accelemed Research Institute	Austin	Texas
United States	Harvard Medical School	Boston	Massachusetts
United States	Institute for Liver Health dba Arizona Liver Health	Chandler	Arizona
United States	University of Virginia	Charlottesville	Virginia
United States	ARcare Center for Clinical Research	Conway	Arkansas
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	AIG Digestive Disease Research	Florham Park	New Jersey
United States	Cure Clinical Research, LLC	Fountain Valley	California
United States	Velocity Clinical Research	Gardena	California
United States	Digestive Health Research	Hermitage	Tennessee
United States	Birmingham Digestive Health Research	Homewood	Alabama
United States	National Research Institute	Huntington Park	California
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Galenus Group	Lehigh Acres	Florida
United States	ARcare Center for Clinical Research	Little Rock	Arkansas
United States	Tandem Clinical Research - New Orleans Area Site	Marrero	Louisiana
United States	Prolive Medical Research	Miami	Florida
United States	Cadena Care Institute, LLC	Poway	California
United States	Central Virginia VA Healthcare System	Richmond	Virginia
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	Digestive Health Research of Southern California	South Bend	Indiana
United States	Impact Research Institute	Waco	Texas
United States	Digestive Health Research of North Texas	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Inventiva Pharma

Countries where clinical trial is conducted

United States,  Belgium,  France,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Absolute change in HbA1c from baseline (Week 0) to Week 24	Date of randomisation until the end of treatment at week 24