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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 ) (NATiV3)

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ClinicalTrials.gov Identifier: NCT04849728
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : December 6, 2023
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 December 6, 2023
Actual Study Start Date  ICMJE August 19, 2021
Estimated Primary Completion Date September 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2023)
  • Resolution of NASH and improvement of fibrosis [ Time Frame: 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
  • Safety Analyses [ Time Frame: 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.
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 Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
Official Title  ICMJE A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis Stages F2 and F3
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 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 1000 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 A and Part B.
    Other Name: Lanifibranor
  • Drug: Placebo
    A total of 1000 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 A and Part B.
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: March 30, 2023)
1000
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2021)
2000
Estimated Study Completion Date  ICMJE September 30, 2026
Estimated Primary Completion Date September 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Prescreening Criteria:

  • Diagnosed with NASH on prior liver biopsy
  • Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound
  • At least 3 of the components of metabolic syndrome

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)
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: Pascaline Clerc 2024998937/0644637545 clinical.contact@inventivapharma.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Czechia,   France,   Germany,   Hungary,   Israel,   Italy,   Mexico,   Netherlands,   Poland,   Portugal,   Puerto Rico,   South Africa,   Spain,   Ukraine,   United Kingdom,   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
Current Responsible Party Inventiva Pharma
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Inventiva Pharma
Original Study Sponsor  ICMJE Same as current
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 December 2023

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