A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )

Phase 3

Recruiting

• Conditions: NASH - Nonalcoholic Steatohepatitis
• Interventions: Drug: IVA337; Drug: Placebo

• Registration Number: NCT04849728
• Lead Sponsor: Inventiva Pharma

Brief Summary

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3

Detailed Description

Primary objectives

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives:

Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology.

Part B To assess the safety of lanifibranor beyond the DBPC period. Secondary objectives

Key secondary objectives of Part 1:

* To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis

* To assess the effect of lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH

Other secondary objectives of both Part 1 and Part 2:

* To assess the effect of lanifibranor on other key histological features of NASH (only for DBPC period)

* To assess the effect of lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period)

* To assess the effect of lanifibranor on liver tests

* To assess the effect of lanifibranor on glycaemic parameters

* To assess the effect of lanifibranor on lipid parameters

* To assess the effect of lanifibranor on liver stiffness and steatosis assessed by elastography.

* To assess the effect of lanifibranor on health-related quality of life

* To assess the safety of lanifibranor

* To assess population PK modeling through plasma levels of lanifibranor using sparse sampling scheme (only for DBPC period)

Study Timeline

• Study First Submitted: 2021-04-16
• Study First Submitted QC: 2021-04-16
• Study First Posted: 2021-04-19
• Study Start: 2021-08-19
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-24
• Last Update Posted: 2024-01-26
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

1. Male or female, aged ≥18 years at the time of signing informed consent

2. Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):

   1. Steatosis score ≥1
   2. Activity score: A3 or A4
   3. Fibrosis score: F2 or F3

3. No qualitative change in dose for the drugs listed below:

   1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
   2. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
   3. Statins: for at least 3 months

4. No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening

5. Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)

6. Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.

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. Positive human immunodeficiency virus (HIV) serology

6. ALT or AST >5 × ULN

7. AST<0.6 ULN if the liver biopsy has to be performed in the scope of the study

8. Abnormal synthetic liver function as defined by Screening central laboratory evaluation

9. Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males

10. Patient currently receiving any approved treatment for NASH or obesity

11. Current or recent history (<5 years) of significant alcohol consumption

12. Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy

    Glycaemia related:

13. HbA1c >9% at Screening

14. Diabetes mellitus other than type 2

15. Current treatment with insulin

16. Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.

    Obesity related:

17. Bariatric surgery: Restrictive procedures are allowed, if performed >6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.

    Cardiovascular related:

18. History of heart failure with reduced left ventricular ejection fraction (LVEF)

19. Atrial fibrillation requiring anticoagulation

20. Unstable heart failure

21. Uncontrolled hypertension at Screening (values >160/100 mm Hg)

    General safety:

22. Women currently breastfeeding

23. Previous exposure to lanifibranor

24. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer

25. Concomitant treatment with PPAR-alpha agonists (fibrates)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lanifibranor (IVA 337) (800 mg/day)	Placebo	2 Lanifibranor tablets 400mg + 1 Placebo to match tablet with food --\> once a day (quaque die, QD)
Matching placebo	Placebo	3 Placebo to match tablets with food --\> once a day (quaque die, QD)
Lanifibranor (IVA 337) (800 mg/day)	IVA337	2 Lanifibranor tablets 400mg + 1 Placebo to match tablet with food --\> once a day (quaque die, QD)
Lanifibranor (IVA 337) (1200 mg/day)	IVA337	3 Lanifibranor tablets 400mg with food --\> once a day (quaque die, QD)

Primary Outcome Measures

Name	Time	Method
Safety Analyses	48 weeks after completion of DBPC period	Part B: ATE: * Using the DBPC on-treatment period, comparing the 2 active arms versus placebo; * Using the DBPC +ATE on treatment periods, assessing the 2 active arms. For adverse events, adjudicated liver events, and DILI and MACE events, in addition to the raw cumulative incidence proportions, the exposure-adjusted incidence rates will be provided based on the time patients are at risk.
Resolution of NASH and improvement of fibrosis	Part A: Date of randomisation until the date of biopsy at Week 72	Part A: DBPC: Resolution of NASH and improvement of fibrosis at Week 72, defined by NASH CRN scores for ballooning of 0 and inflammation of 0 to 1, and fibrosis score ≥1 stage decrease compared to Baseline

Trial Locations

Locations (483)

Pinnacle Research Group; 🇺🇸 Anniston, Alabama, United States

Objective Health - Birmingham Gastroenterology Associates; 🇺🇸 Birmingham, Alabama, United States

Digestive Health Specialist of the Southeast; 🇺🇸 Dothan, Alabama, United States

North Alabama GI Research Center llc; 🇺🇸 Madison, Alabama, United States

The Institute For Liver Health - Chandler; 🇺🇸 Chandler, Arizona, United States

Arizona Liver Health - Peoria; 🇺🇸 Peoria, Arizona, United States

Saint Joseph's Hospital and Medical Center; 🇺🇸 Phoenix, Arizona, United States

Arizona Digestive Health - Sun City; 🇺🇸 Kansas City, Kansas, United States

Adobe Gastroenterology; 🇺🇸 Tucson, Arizona, United States

Arizona Liver Health; 🇺🇸 Tucson, Arizona, United States

Scroll for more (473 remaining)