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)
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| ClinicalTrials.gov Identifier: NCT05232071 |
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Recruitment Status :
Active, not recruiting
First Posted : February 9, 2022
Last Update Posted : February 23, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| NASH - Nonalcoholic Steatohepatitis Diabetes Mellitus, Type 2 | Drug: IVA337 Drug: Placebo Drug: Empagliflozin | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 42 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | June 29, 2022 |
| Estimated Primary Completion Date : | March 30, 2024 |
| Estimated Study Completion Date : | December 31, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Lanifibranor (IVA337) (800 mg/day)
2 Lanifibranor tablets 400 mg with food --> once a day (quaque die, QD)
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Drug: IVA337
800 mg
Other Name: Lanifibranor |
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Placebo Comparator: Matching placebo
2 Placebo to match tablets with food --> once a day (quaque die, QD)
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Drug: Placebo
Placebo to match |
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Experimental: 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)
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Drug: IVA337
800 mg
Other Name: Lanifibranor Drug: Empagliflozin 10 mg
Other Name: Jardiance |
- 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 [ Time Frame: Date of randomisation until the end of treatment at week 24 ]Absolute change in HbA1c from baseline (Week 0) to Week 24
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
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)
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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
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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.
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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:
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05232071
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| Responsible Party: | Inventiva Pharma |
| ClinicalTrials.gov Identifier: | NCT05232071 |
| Other Study ID Numbers: |
337HNAS21016 |
| First Posted: | February 9, 2022 Key Record Dates |
| Last Update Posted: | February 23, 2024 |
| Last Verified: | February 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases |
Liver Diseases Digestive System Diseases Empagliflozin Sodium-Glucose Transporter 2 Inhibitors Molecular Mechanisms of Pharmacological Action Hypoglycemic Agents Physiological Effects of Drugs |