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

NCT ID: NCT05232071

Last Updated: 2024-07-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-29

Study Completion Date

2024-06-04

Brief Summary

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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

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Conditions

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NASH - Nonalcoholic Steatohepatitis Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Lanifibranor (IVA337) (800 mg/day)

2 Lanifibranor tablets 400 mg with food --\> once a day (quaque die, QD)

Group Type EXPERIMENTAL

IVA337

Intervention Type DRUG

800 mg

Matching placebo

2 Placebo to match tablets with food --\> once a day (quaque die, QD)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo to match

Lanifibranor (IVA337) (800 mg/day) plus Empagliflozin (10mg/day)

2 Lanifibranor tablets 400 mg plus 1 Empagliflozin tablet 10mg with food --\> once a day (quaque die, QD)

Group Type EXPERIMENTAL

IVA337

Intervention Type DRUG

800 mg

Empagliflozin

Intervention Type DRUG

10 mg

Interventions

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IVA337

800 mg

Intervention Type DRUG

Placebo

Placebo to match

Intervention Type DRUG

Empagliflozin

10 mg

Intervention Type DRUG

Other Intervention Names

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Lanifibranor Jardiance

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Inventiva Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham Digestive Health Research

Homewood, Alabama, United States

Site Status

Institute for Liver Health dba Arizona Liver Health

Chandler, Arizona, United States

Site Status

ARcare Center for Clinical Research

Conway, Arkansas, United States

Site Status

ARcare Center for Clinical Research

Little Rock, Arkansas, United States

Site Status

Cure Clinical Research, LLC

Fountain Valley, California, United States

Site Status

Velocity Clinical Research

Gardena, California, United States

Site Status

National Research Institute

Huntington Park, California, United States

Site Status

Cadena Care Institute, LLC

Poway, California, United States

Site Status

Florida Research Institute

Lakewood Rch, Florida, United States

Site Status

Galenus Group

Lehigh Acres, Florida, United States

Site Status

Prolive Medical Research

Miami, Florida, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Digestive Health Research of Southern California

South Bend, Indiana, United States

Site Status

Tandem Clinical Research - New Orleans Area Site

Marrero, Louisiana, United States

Site Status

Harvard Medical School

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

AIG Digestive Disease Research

Florham Park, New Jersey, United States

Site Status

Digestive Health Research

Hermitage, Tennessee, United States

Site Status

Accelemed Research Institute

Austin, Texas, United States

Site Status

Dallas Diabetes Research Center

Dallas, Texas, United States

Site Status

American Research Corporation

San Antonio, Texas, United States

Site Status

Diabetes & Glandular Disease Clinic, P.A.

San Antonio, Texas, United States

Site Status

Impact Research Institute

Waco, Texas, United States

Site Status

Digestive Health Research of North Texas

Wichita Falls, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Central Virginia VA Healthcare System

Richmond, Virginia, United States

Site Status

CUB Erasme Hospital

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

AZ Maria Middelares

Ghent, , Belgium

Site Status

UZ GENT

Ghent, , Belgium

Site Status

CHU Angers_Service d'hepatogastro-enterologie

Angers, , France

Site Status

CHU Limoges

Limoges, , France

Site Status

Hopital Saint Antoine

Paris, , France

Site Status

CHU Bordeaux

Pessac, , France

Site Status

Chu Rangueil

Toulouse, , France

Site Status

HGE CHRU Nancy

Vandœuvre-lès-Nancy, , France

Site Status

Amsterdam UMC

Amsterdam, , Netherlands

Site Status

Hull University Teaching Hospital

Hull, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

St Georges Hospital

London, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Belgium France Netherlands United Kingdom

Other Identifiers

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337HNAS21016

Identifier Type: -

Identifier Source: org_study_id

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