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A Phase 3 Study Evaluating Long-term Efficacy and Safety of Lanifibranor in Adult Patients With (NASH) and Fibrosis 2 (F2)/Fibrosis 3 (F3) Stage of Liver Fibrosis (NATiV3)

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ClinicalTrials.gov Identifier: NCT04849728
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : October 26, 2021
Sponsor:
Information provided by (Responsible Party):
Inventiva Pharma

Tracking Information
First Submitted Date  ICMJE April 16, 2021
First Posted Date  ICMJE April 19, 2021
Last Update Posted Date October 26, 2021
Actual Study Start Date  ICMJE August 19, 2021
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2021)
  • Resolution of NASH and improvement of fibrosis [ Time Frame: Part 1: Date of randomisation until the date of biopsy at Week 72 ]
    Part 1: 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
  • Time to first clinical outcome event [ Time Frame: Part 2: Date of randomisation until the End of Study (EoS) date approximately 7 years after first patient randomized ]
    Part 2:
    • Histological progression to cirrhosis (defined as histological confirmation of fibrosis score CRN F4)
    • All-cause mortality
    • Liver transplant
    • Model for End-Stage Liver Disease (MELD) score ≥15
    • New onset ascites requiring treatment
    • Overnight hospitalisation due to hepatic decompensation event(s) including:
      • Hepatic encephalopathy Grade ≥2 (as assessed by West Haven scale)
      • Variceal bleeding
      • Spontaneous bacterial peritonitis (assessed by positive culture or cell count)
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2021)
Resolution of NASH [ Time Frame: Date of randomisation until the date of biopsy at Week 72 ]
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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study Evaluating Long-term Efficacy and Safety of Lanifibranor in Adult Patients With (NASH) and Fibrosis 2 (F2)/Fibrosis 3 (F3) Stage of Liver Fibrosis
Official Title  ICMJE A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Long-term Efficacy and Safety of Lanifibranor in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis 2 (F2)/Fibrosis 3 (F3) Stage of Liver Fibrosis
Brief Summary This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage 2 or 3
Detailed Description

Primary objectives

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage 2 or 3 and consists of 2 parts - Part 1 and Part 2, with the following primary objectives:

Part 1 To assess the effect of lanifibranor compared to placebo on NASH resolution and improvement of fibrosis assessed by liver histology.

Part 2 To assess the effect of lanifibranor compared to placebo on delaying NASH disease progression measured by a composite endpoint that includes progression to cirrhosis, liver-related clinical outcome events, or all-cause death.

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 compared to placebo on other key histological features of NASH
  • To assess the effect of lanifibranor compared to placebo on NASH resolution and improvement of fibrosis in diabetic patients
  • To assess the effect of lanifibranor compared to placebo on liver function tests
  • To assess the effect of lanifibranor compared to placebo on glycaemic parameters
  • To assess the effect of lanifibranor compared to placebo on lipid parameters
  • To assess the effect of lanifibranor compared to placebo on liver stiffness
  • To assess the effect of lanifibranor compared to placebo on health-related quality of life
  • To assess the long-term safety (up to 7 years) of lanifibranor
  • To assess population PK modeling of lanifibranor using sparse sampling scheme
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE NASH - Nonalcoholic Steatohepatitis
Intervention  ICMJE
  • Drug: IVA337
    A total of 2000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part 1 and Part 2.
    Other Name: Lanifibranor
  • Drug: Placebo
    A total of 2000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part 1 and Part 2.
Study Arms  ICMJE
  • Experimental: Lanifibranor (IVA 337) (800 mg/day)
    2 Lanifibranor tablets 400mg + 1 Placebo to match tablet with food --> once a day (quaque die, QD)
    Interventions:
    • Drug: IVA337
    • Drug: Placebo
  • Experimental: Lanifibranor (IVA 337) (1200 mg/day)
    3 Lanifibranor tablets 400mg with food --> once a day (quaque die, QD)
    Intervention: Drug: IVA337
  • Placebo Comparator: Matching placebo
    3 Placebo to match tablets with food --> once a day (quaque die, QD)
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 16, 2021)
2000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2028
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Stable 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): Stable dose for at least 3 months
    2. Vitamin E (if at a dose ≥400 IU/day): Stable dose for at least 6 months
    3. Statins: Stable dose for at least 3 months
  4. All other chronically administered drugs must be stable 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. Abnormal synthetic liver function as defined by Screening central laboratory evaluation
  8. Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males
  9. Patient currently receiving any approved treatment for NASH or obesity
  10. Current or recent history (<5 years) of significant alcohol consumption
  11. 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:

  12. HbA1c >9% at Screening
  13. Diabetes mellitus other than type 2
  14. Current treatment with insulin
  15. Previous or current treatment with PPAR-gamma agonists (thiazolidinediones [TZDs])

    Obesity related:

  16. 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:

  17. History of heart failure with reduced left ventricular ejection fraction (LVEF)
  18. Atrial fibrillation requiring anticoagulation
  19. Unstable heart failure
  20. Uncontrolled hypertension at Screening (values >160/100 mm Hg)

    General safety:

  21. Women currently breastfeeding
  22. Previous exposure to lanifibranor
  23. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
  24. Concomitant treatment with PPAR-alpha agonists (fibrates)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Cooreman, MD 380447500 ext +33 info@inventivapharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04849728
Other Study ID Numbers  ICMJE 337HNAS20011
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inventiva Pharma
Study Sponsor  ICMJE Inventiva Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arun J Sanyal, MD VCU Health, Gastroenterology Hepatology and Nutrition, 1200 West Broad Street, Richmond VA23298, USA
Principal Investigator: Sven Francque, MD Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium
PRS Account Inventiva Pharma
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP